Activated cll cells. Medical search. Frequent questions

ZAP-70 expression is a significant indicator of the survival of lymphocytes and has been notably associated with chronic lymphocytic leukemia (CLL). (wikipedia.org)

ZAP-70 (Zeta-chain-associated protein kinase 70) is a protein normally expressed near the surface membrane of lymphocytes (T cells, natural killer cells, and a subset of B cells). (wikipedia.org)
ZAP-70 was initially discovered in TCR-stimulated Jurkat cells, an immortal line of human T lymphocytes, in 1991. (wikipedia.org)
T lymphocytes are activated by engagement of the T cell receptor with processed antigen fragments presented by professional antigen presenting cells (i.e. macrophages, dendritic cells, Langerhans cells and B cells) via the MHC. (wikipedia.org)
The disease is most commonly diagnosed among people age 50 or older and is characterized by the accumulation of functionally immature white blood cells (lymphocytes) in the bone marrow, blood, lymph tissue, and other organs. (worldpharmanews.com)
Two types of lymphocytes are present in the blood, B cells and T cells. (worldpharmanews.com)
First described in 1975, NK cells were initially identified as a distinct sub-population of lymphocytes by their capacity to spontaneously lyse tumor cells ( 1 ). (frontiersin.org)
Chronic lymphocytic leukemia (CLL) is characterized by progressive accumulation of phenotypically mature malignant B lymphocytes. (msdmanuals.com)
These B lymphocytes produce multispecific autoantibodies and generate most of the B chronic lymphocytic leukemias (CLL). (biomedcentral.com)
Intro Chronic lymphocytic leukemia (CLL) probably the most common type of adult leukemia in Traditional western countries is seen as a the progressive build up of phenotypically adult monoclonal LY2784544 (Gandotinib) B lymphocytes in the peripheral bloodstream lymph nodes and bone tissue marrow. (cell-signaling-pathways.com)
In CLL, the body produces too many lymphocytes, a type of white blood cell that helps fight infection. (cancercare.org)
However, it remains unclear whether CLL-B cells aberrantly acquire ZAP-70 expression during the transformation process or whether ZAP-70 may be expressed under certain conditions in normal human B-lymphocytes. (elsevierpure.com)
Our data demonstrate that ZAP-70 is expressed in a subpopulation of tonsillar and splenic normal B-lymphocytes that express an activated phenotype. (elsevierpure.com)
Background: The PI3K pathway is a central pro-survival mechanism in chronic lymphocytic leukemia (CLL), with expression of the delta isoform of PI3K largely restricted to lymphocytes. (duke.edu)
Herein, we evaluate the in vitro effect of TGR-1202 on CLL lymphocytes, specifically evaluating differences between 17pdel CLL and non-17pdel CLL samples. (duke.edu)
CLL lymphocytes were isolated using negative selection yielding greater than 95% purity. (duke.edu)
TGR-1202 induced cytotoxicity and apoptosis in a dose-dependent manner in concentrations between 4 nM and 25 μM with no significant difference in results observed between normal CLL lymphocytes those that had 17pdel cytogenetics. (duke.edu)
We also found that TGR-1202 significantly suppressed AKT phosphorylation in CLL lymphocytes. (duke.edu)
Conclusions: TGR-1202 is a potent PI3K-δ inhibitor that suppresses AKT phosphorylation and induces apoptosis-dependent cytotoxicity in primary CLL lymphocytes, both with favorable and adverse cytogenetics. (duke.edu)
We observed that higher concentrations of TGR-1202 were required to induce cytotoxicity in non-17pdel CLL lymphocytes on average, than in 17pdel CLL. (duke.edu)
Chronic lymphocytic leukemia (CLL) is a B-cell hematological malignancy characterized by the clonal expansion and accumulation of morphologically mature B-lymphocytes in peripheral blood, bone marrow, and secondary lymphoid tissues. (oncotarget.com)
The disease is usually characterized by the accumulation of monoclonal CD5+ B lymphocytes arrested in the G0/G1 phases of the cell cycle. (eotp.org)
PI3Kδ and γ, for example, are preferentially expressed in B lymphocytes and are often constitutively activated in B-cell malignancies. (proedcomblog.com)
FI-C3b labeled 17.6% +/- 6.0% of peripheral blood mononuclear cells (PBM) from 20 normal subjects, which, when separated by the FACS, consisted of B lymphocytes and approximately 5% monocytes. (ashpublications.org)
This agent binds CD20 on lymphocytes and induces apoptosis as well as initiating complement-mediated killing of bound cells. (medscape.com)
The CD20 antigen is expressed on the surface of pre-B cells and mature B lymphocytes. (medscape.com)
Lymphocytic interstitial pneumonia (LIP) is a syndrome of fever, cough, and dyspnea, with bibasilar pulmonary infiltrates consisting of dense interstitial accumulations of lymphocytes and plasma cells. (medscape.com)
CLL is considered the most common form of leukemia in adults and is a type of cancer that starts in white blood cells, known as lymphocytes. (lu.se)

In accordance, CIGB-300 decreases the viability and proliferation of CLL cell lines, promotes apoptosis of primary leukemia cells and displays antitumor efficacy in a xenograft mouse model of human CLL. (oncotarget.com)
Assessment of leukemia cells of ROR1 TCL1 versus TCL1 mice for activation of AKT, proliferation, and spontaneous apoptosis. (rawveronica.com)
In MSC and suspension system cocultures PI-103 and PIK-90 were potent inducers of CLL cell apoptosis. (cell-signaling-pathways.com)
Primary CLL cells were incubated with serial dilutions of TGR-1202 tested for apoptosis by activated caspase-3 and 7AAD staining measured by flow cytometry. (duke.edu)
Furthermore, Wnt inhibitor ethacrynic acid (EA) induced both apoptosis and necroptosis in primary CLL cells. (oncotarget.com)
BCR is important for the proliferation, differentiation and apoptosis of B cells [ 3 ]. (biomedcentral.com)
However, there are conflicting results whether exposure to anti-IgM in vitro promotes or suppresses apoptosis in CLL cells [ 6 ] and other signals provided by the tumor microenvironment likely determines the outcome [ 7 ]. (biomedcentral.com)
This is particularly true for galectin family members because changes in their expression levels correlate with alterations in cancer cell growth, apoptosis, and cell-cell and cell-matrix interactions. (fdocuments.net)
C. Representative dot-plot depicting the read-out for lysed leukemic cells of panels Apoptosis Inhibitor (M50054) A and B. Percentages denote the proportion of lysed leukemic cells, thus staining positive for the Live/Dead stain. (euromed2016.com)
Previous studies have show that monocytes upon conversation with CD20 mAb-opsonized CLL cells may shave off or extract the antibody-antigen complex from the CLL cells, a mechanism known as trogocytosis, thus Apoptosis Inhibitor (M50054) reducing the amount of antibody bound to the CLL cells and limiting NK cell-mediated ADCC [17, 18]. (euromed2016.com)
The primary pathogenic event that causes the generation of aberrant B cells remains to be decided, but impaired apoptosis results in increased survival of circulating CLL cells. (eotp.org)
Apoptosis can be induced via two main pathways: interference with mitochondrial function, also called the intrinsic pathway, or triggering of cell surface death receptors, also called the extrinsic pathway (2,3). (eotp.org)
Thus, the induction of apoptosis via the extrinsic pathway requires additional cleavage of the proapoptotic Bcl-2 family member BID through caspase 8, which activates the intrinsic pathway and subsequently apoptosis (type II cell mechanism) (7,8). (eotp.org)
In malignant cells, HDACIs induce apoptosis SMIP004 by upregulation of proapoptotic and repression of antiapoptotic genes (14C16). (eotp.org)
It was our goal to further elucidate the effects of VPA on apoptosis in these SMIP004 cells. (eotp.org)
One method is to target senescent T cells which have selective apoptosis function. (hindawi.com)
[3] This kinase inhibition shuts down BCR signaling, reduces B cell proliferation, and promotes apoptosis of leukemic cells. (championsoncology.com)
Its roles include regulation of proliferation, promotion of immune system and activation of apoptosis in B cells. (intechopen.com)
In these cells, IL-21 does not promote proliferation but enhances apoptosis and chemotaxis. (intechopen.com)

However, as tumors progress, cancerous cells develop immunosuppressive mechanisms that circumvent NK cell-mediated killing, allowing for tumor escape and proliferation. (frontiersin.org)
Here we sought to further understand the effects of idelalisib and duvelisib in vitro, and demonstrate that both idelalisib and duvelisib can inhibit T cell proliferation as well as Th1 and Treg differentiation in vitro, while promoting Th2 and Th17 differentiation. (nature.com)
The progression of chronic lymphocytic leukemia (CLL) is strongly associated with the modification of diverse immune cell populations to create a niche appropriate for the proliferation and survival of leukemic B cells. (biomedcentral.com)
These data suggest that manifestation of ROR1 may promote CD5+B220low B-cell proliferation and survival. (rawveronica.com)
The progressive accumulation of leukemic cells is mostly ascribed to extended cellular survival rather than excessive cellular proliferation [ 1 ]. (oncotarget.com)
These drugs inhibit Bruton tyrosine kinase (BTK) or phosphatidylinositol 3-kinase (PI3K), key components of the B-cell receptor signaling pathway that is crucial for proliferation, survival and homing of malignant B cells. (haematologica.org)
14 Inhibition of BTK in malignant B cells induces diminished proliferation, decreased survival and impaired adhesion and migration of the malignant B cells to their growth-promoting microenvironment. (haematologica.org)
1] Unmutated CLL is more aggressive than mutated CLL, and the presence of these abnormal IGHV sequences, a part of B cell receptors (BCR), leads to abnormal BCR signaling and the uncontrolled proliferation of leukemic cells. (championsoncology.com)
[2] Notably, BTK has been shown to be constitutively active in CLL and drives both leukemic cell proliferation and lymph node homing. (championsoncology.com)
Under normal conditions, this pathway leads to controlled B cell proliferation and differentiation, however, this same pathway leads to uncontrolled B cell proliferation in malignancies, such as CLL. (championsoncology.com)
This disease is characterized by the uncontrolled proliferation of abnormal monoclonal plasma cells in the bone marrow. (lls.org)

Mice lacking PI3Kγ show increased CD8 T cell activation and cytotoxicity due to transcriptional activation of NFκB and inhibition of C/EBPβ in macrophages within the microenvironment [ 9 ]. (nature.com)
It is still unclear which molecular factors and cell types are involved in shaping neutrophil function and phenotype in the CLL microenvironment. (biomedcentral.com)
To investigate the interrelation between Treg and neutrophils in the leukemia microenvironment, we performed experiments using TCL1-injected DEREG mice with Treg depletion or RAG2KO mice with adoptively transferred TCL1 cells alone or together with Treg. (biomedcentral.com)
The immunosuppressive CLL microenvironment supports disease progression, contributes to CLL escape from immune surveillance and significantly destabilizes the whole immune response of a CLL patient [ 8 ]. (biomedcentral.com)
consequently additional CLL-microenvironment relationships may represent alternative therapeutic targets. (cell-signaling-pathways.com)
Inhibition of PI3K δ induces disruption of interactions between malignant B cells and their microenvironment. (haematologica.org)
This mechanism of cell death may be common among the tyrosine kinase inhibitors.26 The evidence that ZAP-70 expression sensitizes cells to gefitinib and that gefitinib targets the BCR pathway both indicate that this drug may have activity in the microenvironment. (sciencepop.org)

Additionally, a 11-year prospective cohort study of Japanese inhabitants linked low peripheral-blood NK cell cytotoxicity with increased cancer risk ( 12 ). (frontiersin.org)
The cytotoxicity receptor NKG2D is downregulated, and the killing capacity through this receptor was markedly reduced in CLL-derived NK cells. (vu.nl)
CAT CAR-T cells showed greater cytotoxicity and proliferative responses in vitro and maintained long-lived molecular remissions in children with relapsed or refractory ALL, as demonstrated in the CARPALL study 3 . (nature.com)
The PI3K-δ inhibitor TGR-1202 induces cytotoxicity and inhibits phosphorylation of AKT in 17p deleted and non-17p deleted CLL cells in vitro. (duke.edu)
EA also enhanced the cytotoxicity of both fludarabine and cyclophosphamide against CLL cells in vitro. (oncotarget.com)
In accordance with earlier reports [22, 23], NK cells isolated from CLL patients induced significant CLL cell death in the presence of RTX with only minor cytotoxicity in the absence of a linking antibody. (euromed2016.com)
Monocytes failed to exert substantial RTX-dependent cytotoxicity against CLL cells. (euromed2016.com)
The immune effector cell mechanisms include antibody-dependent cellular cytotoxicity and antibody-dependent cellular phagocytosis. (medscape.com)

Increased expression of ZAP-70 in B cell malignancies is correlated with increased association between malignant B cells and the immune environment, suggesting a complex role for ZAP-70 in B cell signaling. (wikipedia.org)
PI3Kδ inhibitors are approved for the therapy of B cell malignancies, but their clinical use has been limited by unpredictable autoimmune toxicity, despite promising efficacy and evidence that toxicity is associated with improved clinical outcomes. (nature.com)
Adoptive switch of allogeneic pure killer (NK) cells is changing into a reputable immunotherapy for hematological malignancies. (nfkb-p65.info)
It is unclear whether one can generalize from two adult patients treated for CLL to other hematological malignancies and patient groups, in particular to childhood ALL, or to other CAR-T cell products. (nature.com)
A Phase I trial with once-daily TGR-1202 is currently ongoing in patients with hematologic malignancies, including CLL. (duke.edu)
Small lymphocytic lymphoma/chronic lymphocytic leukemia (SLL/CLL) and marginal zone lymphoma (MZL) are indolent lymphoid malignancies that arise from mature B cells. (biomedcentral.com)
In contrast SMIP004 to most other hematological malignancies, CLL cells have a negligibly low fraction of growing cells. (eotp.org)
1 Consequently small-molecule PI3K inhibitors with varying levels of selectivity for several PI3K isoforms have been developed, mainly for B-cell malignancies like chronic lymphocytic leukemia (CLL), and indolent non-Hodgkin's lymphomas (iNHL), including marginal zone lymphoma (MZL) or follicular lymphoma (FL). (proedcomblog.com)
The use of novel B-cell receptor signaling inhibitors results in high response rates and long progression-free survival in patients with indolent B-cell malignancies, such as chronic lymphocytic leukemia, follicular lymphoma, mantle cell lymphoma and Waldenström macroglobulinemia. (haematologica.org)
Ibrutinib, the first-in-class inhibitor of Bruton tyrosine kinase, and idelalisib, the first-in-class inhibitor of phosphatidylinositol 3-kinase δ , have recently been approved for the treatment of several indolent B-cell malignancies. (haematologica.org)
Recently, a new class of drugs has been introduced for the treatment of various B-cell malignancies, including chronic lymphocytic leukemia (CLL), small lymphocytic lymphoma, follicular lymphoma, mantle cell lymphoma, marginal zone lymphoma and Waldenström macroglobulinemia. (haematologica.org)
T cell immune protection plays a pivotal role in the treatment of patients with hematological malignancies. (hindawi.com)
However, T cell exhaustion might lead to the possibility of immune escape of hematological malignancies. (hindawi.com)
Adoptive cell therapy (ACT) with chimeric antigen receptor T (CAR-T) cells can restore the activity of exhausted T cell through reprogramming and is widely used in the treatment of relapsed/refractory (r/r) hematological malignancies. (hindawi.com)
However, CAR-T cells can also produce some adverse events after treatment of hematological malignancies, such as cytokine release syndrome (CRS), neurotoxicity, and on-target/off-tumor toxicity, which may cause systemic immune stress inflammation, destruction of the blood-brain barrier, and even normal tissue damage. (hindawi.com)
Traditionally, the treatment of hematological malignancies is administrated by chemotherapy, radiotherapy, and stem cell transplantation. (hindawi.com)
It is noted that T cell has great potential for immunotherapy of hematological malignancies. (hindawi.com)
In addition, the isolation and storage of umbilical cord blood hematopoietic stem cells have been used to rebuild the immune system for the treatment of hematological malignancies and might be promising for the dynamic equilibrium expansion of functional T cells [ 12 ]. (hindawi.com)

The recent FDA approvals of the programmed cell death protein 1 (PD-1)-targeted checkpoint inhibitors pembrolizumab and nivolumab mark the latest successes in the rapidly expanding field of cancer immunotherapies. (frontiersin.org)
Cytokines, cancer vaccines, adoptive cell transfers, and especially checkpoint inhibitors constitute valuable elements in the immunotherapeutic armamentarium. (frontiersin.org)
We further demonstrate directly using intracellular flow cytometry that autoimmune toxicity in patients is associated with higher absolute numbers of CD4 and CD8 T cells with Th17 differentiation in peripheral blood prior to therapy, and that gastrointestinal tissues from patients with active autoimmune complications of PI3Kδ inhibitors show infiltration with Th17 + T cells. (nature.com)
Although targeted inhibitors have transformed CLL therapy [ 1 ], patients are increasingly relapsing after both BTK inhibitors and the BCL-2 inhibitor venetoclax. (nature.com)
Our studies provide pre-clinical support for the testing and possible inclusion of CK2 inhibitors in the clinical arsenal against CLL. (oncotarget.com)
Collectively our data demonstrate that p110α inhibitors LY2784544 (Gandotinib) antagonize stromal cell-derived migration success and drug-resistance indicators and therefore give a logical to explore the restorative activity of the promising real estate agents in LY2784544 (Gandotinib) CLL. (cell-signaling-pathways.com)
Clinical evaluation of PI3K-δ inhibitors, such as idelalisib, in CLL patients has been promising. (duke.edu)
In this review we discuss the most commonly reported and/or most clinically relevant adverse events associated with these B-cell receptor inhibitors, with special emphasis on recommendations for their management. (haematologica.org)
Richter transformation is not discussed extensively as it is not an adverse event, although it is important to be aware that Richter transformation is occasionally observed during treatment with B-cell receptor inhibitors. (haematologica.org)
The role of BTK in CLL has drawn researchers to develop BTK inhibitors, such as ibrutinib - an FDA (Food and Drug Administration) [5] and EMA (European Medicines Agency) [6] - approved CLL treatment. (championsoncology.com)
[3] Next-generation, reversible BTK inhibitors, such as ARQ 531, are currently being developed for relapsed/refractory CLL. (championsoncology.com)

However, clinical responses have been disappointingly low in certain Non-Hodgkin lymphomas (NHLs) including chronic lymphocytic leukaemia (CLL). (kcl.ac.uk)

The term "oncotarget" encompasses all molecules, pathways, cellular functions, cell types, and even tissues that can be viewed as targets relevant to cancer as well as other diseases. (oncotarget.com)
Fig. 1 Canonical and noncanonical NF-κB signaling pathways in resting vs. receptor-stimulated cells. (xiahepublishing.com)
The AMP-activated protein kinase is an enzyme and a protein that may play a regulatory role in several metabolic pathways. (biotechpeptides.com)
Knowledge about signaling pathways in malignant cells may provide prognostic and diagnostic information in addition to identify potential molecular targets for therapy. (biomedcentral.com)
Single-cell phospho-specific flow cytometry for detection of basal as well as activation-induced phosphorylation of signaling proteins in distinct cell populations can be used to identify aberrant signaling pathways. (biomedcentral.com)
Therefore, signaling pathways that are required for normal B cell maturation and function are likely disturbed in SLL/CLL and MZL. (biomedcentral.com)
These signaling pathways include the signals propagated through the B-cell receptor (BCR), CD40 and cytokine receptors. (biomedcentral.com)
Investigating the pathways whereby IL-4 promoted Notch1/2 activation in CLL cells independent of Jagged1, we found that PI3Kδ/AKT and PKCδ were involved in upregulating Notch1 and Notch2 proteins, respectively. (unipg.it)
They have long been recognized as one of the most frequently aberrantly activated pathways in cancer, making this a "holy grail" drug target. (proedcomblog.com)
PI3K is a cytoplasmic tyrosine kinase involved in various signaling pathways, most importantly activating the AKT/mTOR pathway. (haematologica.org)
Mediation may be (1) through engagement of immune effector cells, (2) by directly activating intracellular death-signaling pathways, and/or (3) by activation of the complement cascade. (medscape.com)
BTK is a signaling molecule of the B-cell antigen receptor (BCR) and cytokine receptor pathways. (medscape.com)
[4] Lyn and Syk phosphorylate BTK to activate multiple non-receptor protein tyrosine kinase signaling pathways, including NF-κB, MAPK, and phospholipase C gamma (PLCγ). (championsoncology.com)
This pathway is usually a Dimebon dihydrochloride key mechanism for cell survival in CLL.4 5 Upon activation of the BCR tyrosine kinase Lyn phosphorylates and activates Syk leading to activation of downstream signaling pathways and upregulation of anti-apoptotic proteins such as Mcl-1. (sciencepop.org)
In this chapter, we will focus on IL-21's biological effects and signaling pathways as well as discuss the potential implications and applications of IL-21 in leukemia cells. (intechopen.com)
IL-21 activates both the Raf-ERK-MAPK and the Jak/STAT signaling pathways. (intechopen.com)

It is most prominently known to be recruited upon antigen binding to the T cell receptor (TCR), and it plays a critical role in T cell signaling. (wikipedia.org)
The T cell receptor has no innate enzymatic activity. (wikipedia.org)
ZAP-70 is a critical cytoplasmic tyrosine kinase that initiates a signal pathway downstream of an activated T cell receptor. (wikipedia.org)
Upon this activation, the TCR co-receptor CD4 (expressed on T helper cells) or CD8 (expressed on cytotoxic T cells) binds to the MHC, activating the co-receptor associated tyrosine kinase Lck. (wikipedia.org)
This is a monoclonal antibody that inhibits something called ROR1, which is an orphan receptor kinase that is expressed in CLL cells but not expressed in normal B cells or normal adult tissues. (onclive.com)
Some groups, including the group at Ohio State University, have also shown, interestingly, that overexpression of exportin-1 leads to other ways to activate the B-cell receptor signaling pathway. (onclive.com)
In particular, Treg affect the expression of CD62L and IL-4 receptor in neutrophils, both of which are crucial for the function of these cells. (biomedcentral.com)
In the context of relapsed and refractory childhood pre-B cell acute lymphoblastic leukemia (R/R B-ALL), CD19-targeting chimeric antigen receptor (CAR)-T cells often induce durable remissions, which requires the persistence of CAR-T cells. (nature.com)
In this study, we systematically analyzed CD19 CAR-T cells of 10 children with R/R B-ALL enrolled in the CARPALL trial via high-throughput single-cell gene expression and T cell receptor sequencing of infusion products and serial blood and bone marrow samples up to 5 years after infusion. (nature.com)
The advent of CD19 chimeric antigen receptor (CAR)-T cell therapy in recent years has transformed the treatment of intractable ALL 2 . (nature.com)
Receptor tyrosine kinase-like orphan receptor 1 (ROR1) is a type 1 proteins expressed on chronic lymphocytic leukemia (CLL) B cells, however, not on regular postpartum tissue. (rawveronica.com)
Finally, we show that phosphorylation of ZAP-70 occurs in tonsillar B cells with stimulation through the B-cell receptor. (elsevierpure.com)
In various proinflammatory cytokine-stimulated cells, ligand-receptor interactions initially activate TAK1. (xiahepublishing.com)
B-cell receptor (BCR) and co-receptor CD40 signaling is essential for normal B cells, and there is increasing evidence that signaling via BCR and CD40 plays an important role in the pathogenesis of B-cell lymphoma. (biomedcentral.com)
A panel of 9 stimulation conditions targeting B and T cells, including crosslinking of the B cell receptor (BCR), CD40 ligand and interleukins in combination with 12 matching phospho-protein readouts was used to study signaling. (biomedcentral.com)
Some cell SMIP004 types produce insufficient amounts of active caspase 8 at the receptor level. (eotp.org)
The most active T cell endogenous inhibitory pathway is the immunoglobulin superfamily such as CD28/cytotoxic T lymphocyte antigen-4 (CTLA-4): B7-1/B7-2 receptor/ligand grouping, which plays a central role in coordinating immune responses [ 7 , 8 ]. (hindawi.com)
ZAP-70 is usually a member of the Syk family of protein tyrosine kinases and is normally involved in signal transduction of the T-cell receptor in T cells. (sciencepop.org)
ZAP-70 overexpression in malignant B cells such as CLL cells enhances the B-cell receptor (BCR) pathway. (sciencepop.org)

Targeting chronic lymphocytic leukemia cells in the tumor microenviroment: A review of the in vitro and clinical trials to date. (wjgnet.com)
Thus, when cultured alone without special treatment, CLL cells do not proliferate under in vitro conditions. (biomedcentral.com)
CLL cells rely on overexpression and hyperactivation of the ubiquitous serine/threonine protein kinase CK2 for their viability in vitro. (oncotarget.com)
Furthermore, ZAP-70 expression can be induced in vitro upon stimulation of blood and tonsillar B cells. (elsevierpure.com)

Due to this, T cell receptors rely on signaling molecules to transduce a signal from the cell membrane. (wikipedia.org)
NK cell activation and the triggering of effector functions is governed by a complex set of activating and inhibitory receptors. (frontiersin.org)
Here, we review tumor-NK cell interactions, discuss the mechanisms by which NK cells generate an antitumor immune response, and discuss NK cell-based therapeutic strategies targeting activating, inhibitory, and co-stimulatory receptors. (frontiersin.org)
However, CD56 dim NK cells can produce cytokines, specifically IFN-γ, after cell triggering via NKp46 of NKp30 activating receptors or after stimulation with combinations of IL-2, IL-12, and IL-15 ( 7 ). (frontiersin.org)
Here, we studied the expression of activating and inhibitory receptors on CLL-derived and healthy control (HC) NK cells, and their functional response towards several stimuli.NK cells from CLL patients have an increased maturation stage, with an expansion of NKG2C + NK cells in CMV seropositive individuals. (vu.nl)
In activating cells, NF-κB signaling is activated through a series of signaling cascades, following the ligation of various cell surface receptors with paired ligands. (xiahepublishing.com)
The canonical pathway is activated by signals from various immune-related receptors. (xiahepublishing.com)

The treatment landscape in B-cell lymphoma will potentially be redefined by CD20 x CD3 bispecific antibodies, such as plamotamab, and the best outcomes for patients will require creative combination approaches using complementary mechanisms of action. (pharmiweb.com)
In parallel, Xencor will continue, at its own expense, a previously announced clinical collaboration to evaluate the combination of plamotamab, tafasitamab and lenalidomide in patients with B-cell lymphoma, including a Phase 2 trial in relapsed or refractory diffuse large B-cell lymphoma anticipated to start in late 2021 or early 2022. (pharmiweb.com)
We have completed a phase I trial and are now initiating a phase II trial to combine this with ibrutinib for treating patients with CLL or patients with mantle cell lymphoma. (onclive.com)
About 2 to 10% of CLL cases develop into diffuse large B-cell lymphoma (called Richter's transformation). (msdmanuals.com)
Venetoclax (Venclexta) targets the B-cell lymphoma 2 (BCL-2) protein, leading to the death of CLL cells. (cancercare.org)
The aim of this study was to investigate basal and induced signaling in lymphoma B cells and infiltrating T cells in single-cell suspensions of biopsies from small cell lymphocytic lymphoma/chronic lymphocytic leukemia (SLL/CLL) and marginal zone lymphoma (MZL) patients. (biomedcentral.com)
Similarly, CD40L-induced p-ERK and p-p38 were also significantly reduced in lymphoma B cells, whereas p-p65 (NF-κB) was equal to that of normal B cells. (biomedcentral.com)
Intro Mantle cell lymphoma (MCL) can be an intense, incurable largely, subtype of non-Hodgkin lymphoma (NHL).1,2 The hereditary hallmark of MCL may be the chromosomal translocation t(11;14)(q13;q32), which leads to Cyclin-D1 overexpression. (nsdfu.org)
5 years.21,22 Unlike MCL, ibrutinibs activity in chronic lymphocytic leukemia (CLL) and activated B-cell-like diffuse huge B-cell lymphoma (ABC-DLBCL) is in keeping with the documented part of BCR signaling in these illnesses. (nsdfu.org)
Ibrutinib is currently approved for the treatment of mantle cell lymphoma in patients who have received at least one prior therapy, CLL, Waldenström macroglobulinemia [United States Federal Drug Agency (FDA), European Medicine Agency (EMA)] and marginal zone lymphoma (FDA), and idelalisib is approved for previously treated CLL in combination with rituximab and for follicular lymphoma and small lymphocytic lymphoma in patients who have received at least two prior therapies (FDA, EMA). (haematologica.org)
In this review, we aim to summarize the composition of CAR-T cell and its application in the treatment of acute lymphocytic leukemia (ALL), chronic lymphocytic leukemia (CLL), non-Hodgkin's lymphoma (NHL), Hodgkin's lymphoma (HL), multiple myeloma (MM), and acute myeloid leukemia (AML). (hindawi.com)
This phase II/III trial compares the side effects and activity of oral azacitidine in combination with the standard drug therapy (reduced dose rituximab-cyclophosphamide, doxorubicin, vincristine, and prednisone [R-miniCHOP]) versus R-miniCHOP alone in treating patients 75 years or older with newly diagnosed diffuse large B cell lymphoma . (uci.edu)
R-miniCHOP includes a monoclonal antibody (a type of protein), called rituximab, which attaches to the lymphoma cells and may help the immune system kill these cells. (uci.edu)
Participants must have histologically or cytologically confirmed diffuse large B-cell lymphoma (DLBCL), Ann Arbor Stage IIX (bulky), III or IV. (uci.edu)
One of the more recent approvals for MM came July 2019, when Xpovio (Selinexor) was approved for relapsed or refractory multiple myeloma (R/R MM). This drug has received extensive support from LLS: over $4M in 9 grants for acute myeloid leukemia, chronic lymphocytic leukemia, diffuse large B-cell lymphoma and for multiple myeloma. (lls.org)
Mutations of the B-cell CLL/lymphoma 6 ( BCL-6 or zinc finger protein 51) gene have been associated with LIP and mucosa-associated lymphoid tissue (MALT) lymphoma. (medscape.com)
This enabled identification of TFs that can be uniquely associated to the tumor cells of chronic lymphocytic leukemia (CLL), diffuse large B-cell lymphoma (DLBCL), follicular lymphoma (FL), hairy cell leukemia (HCL), and mantle cell lymphoma (MCL). (lu.se)

The importance of ZAP-70 in T cell activation was determined when comparing ZAP-70 expression in patients with SCID (severe combined immunodeficiency). (wikipedia.org)
CLL patients that are positive for the marker ZAP-70 have an average survival of 8 years, whereas those that are negative for ZAP-70 have an average survival of more than 25 years. (wikipedia.org)
Patients afflicted with combined immunodeficiency have a normal lymphocyte count, but they have low concentrations of T helper cells and cytotoxic T cells. (wikipedia.org)
The European Commission has granted marketing authorization to MabCampath® (alemtuzumab) for the treatment of patients with B-cell chronic lymphocytic leukemia (B-CLL) for whom fludarabine combination chemotherapy is not appropriate. (worldpharmanews.com)
With its demonstrated efficacy and manageable safety profile, MabCampath has the potential to become an important treatment option in Europe for patients with B-CLL for whom fludarabine combination chemotherapy is not appropriate. (worldpharmanews.com)
The decision by the European Commission to grant extended marketing authorization to MabCampath was based on data from the CAM307 study, an international open-label Phase III randomized trial comparing MabCampath with chlorambucil in previously untreated patients with B-CLL. (worldpharmanews.com)
The European Union label extension of MabCampath for patients with B-CLL is a prime example of this. (worldpharmanews.com)
Campath was initially approved in 2001 under accelerated approval regulations for the treatment of B-CLL in patients who have been treated with alkylating agents and who have failed fludarabine therapy. (worldpharmanews.com)
It is certainly an exciting, gratifying time to be treating patients with CLL, with new therapies and new combinations that are highly active. (onclive.com)
Prior phenotypic evaluation by CyTOF has identified increases in activated CD8 T cells with activation of Th17 T cells, as well as decreases in Tregs, particularly in patients with toxicity. (nature.com)
These same tissues show depletion of Tregs as compared to CLL patients without toxicity, suggesting that loss of Tregs may be permissive for Th17 activation to lead to autoimmune toxicity. (nature.com)
Impaired neutrophil activity is an important issue in chronic lymphocytic leukemia (CLL), as it contributes to a dysfunctional immune response leading to life-threatening infections in patients. (biomedcentral.com)
BERKELEY, Calif., April 17, 2023 (GLOBE NEWSWIRE) -- Caribou Biosciences, Inc. (Nasdaq: CRBU), a leading clinical-stage CRISPR genome-editing biopharmaceutical company, today presents a poster of preclinical data demonstrating the promise of CB-012, a next-generation CRISPR-edited allogeneic anti-CLL-1 CAR-T cell therapy, as a therapeutic candidate for adult patients with relapsed or refractory acute myeloid leukemia (r/r AML). (cariboubio.com)
Recently, we and others have shown that leukemia cells from CLL patients display higher CK2 expression and activity than normal B cells, leading to inhibition of PTEN and activation of PI3K signaling pathway [ 9 , 10 ], which is required for CLL cell survival [ 11 - 13 ]. (oncotarget.com)
This persistence signature was also detected in two adult patients with chronic lymphocytic leukemia with decade-long remissions who received a different CD19 CAR-T cell product. (nature.com)
We studied 15 consecutive patients with high-risk or relapsed CD19 + B-ALL treated with CD19 CAR-T cell therapy on the CARPALL study ( NCT02443831 ) and in whom adequate CAR-T cells could be isolated for subsequent analyses from cryopreserved samples of blood or bone marrow. (nature.com)
Recently, leukemic cells from some patients with B-cell chronic lymphocytic leukemia (B-CLL) were shown to express ZAP-70. (elsevierpure.com)
CLL patients with 17p deletion (17pdel) have displayed inferior responses to chemo-immunotherapy, and we hypothesized that inhibiting the PI3K/AKT pathway would be equally efficacious in patients with and without 17pdel. (duke.edu)
Methods: We collected blood from CLL patients seen at the Duke Center for CLL and enrolled in IRB approved protocols at the Duke University and Durham VA Medical Centers. (duke.edu)
Our initial observations suggest that clinical evaluation of TGR-1202 enriched in CLL patients with 17pdel may be warranted. (duke.edu)
Patients may benefit from increased appetite, disappearance of swollen lymph nodes, and improvement in normal blood cell counts. (chemoexperts.com)
Imaging may or may not be needed for patients with CLL. (chemoexperts.com)
In this study, we determined LEF1 gene expression levels in CLL ( n = 197) and monoclonal B-cell lymphocytosis (MBL) ( n = 6) patients through real-time RT-PCR. (oncotarget.com)
LEF1 was significantly up-regulated in both MBL and CLL patients compared with normal B cells. (oncotarget.com)
Treatment-free survival (TFS) time and overall survival (OS) time were much longer in CLL patients with low LEF1 expression than in those with high LEF1 levels. (oncotarget.com)
Our results showed, for the first time, that high LEF1 expression is associated with poor survival for CLL patients. (oncotarget.com)
Investigation of aberrantly activated genes with prognostic relevance in CLL may help to identify those patients with a poorer prognosis and to develop novel therapeutic targets for CLL. (oncotarget.com)
Samples from untreated SLL/CLL and MZL patients were examined for basal and activation induced signaling by phospho-specific flow cytometry. (biomedcentral.com)
Malignant B cells from SLL/CLL patients had higher basal levels of phosphorylated (p)-SFKs, p-PLCγ, p-ERK, p-p38, p-p65 (NF-κB), p-STAT5 and p-STAT6, compared to healthy donor B cells. (biomedcentral.com)
BCR signaling and CD40L-induced p-p38 was suppressed in malignant B cells from SLL/CLL and MZL patients. (biomedcentral.com)
For decades, chemotherapy was considered to be the only approach in the treatment of patients with advanced or accelerated CLL. (eotp.org)
The use of chemotherapy in CLL is limited, however, because of rapidly developing resistance and partial unresponsiveness of patients with p53 abnormalities (9,10). (eotp.org)
Mononuclear cells from normal human subjects and patients with chronic lymphocytic leukemia (CLL), chronic lymphosarcoma cell leukemia (LCL), and hairy cell leukemia (HCL) were labeled with fluoresceinated, purified human C3b (FI-C3b) and analyzed using the fluorescence- activated cell sorter (FACS). (ashpublications.org)
Similarly, CR+ mononuclear cells from five patients with HCL and three patients with LCL displayed more homogeneous FI-C3b labeling than normal CR+ PBM. (ashpublications.org)
CLL with deletion of 17p) or elderly or comorbid patients unfit for immunochemotherapy. (haematologica.org)
Ibrutinib is indicated for CLL including patients who are treatment-naïve or have been previously treated. (medscape.com)
It is also indicated for patients who carry a deletion in chromosome 17 (del 17p CLL), which is associated with poor responses to standard treatment. (medscape.com)
It is also indicated as extended treatment (as a single agent) for patients who are in complete or partial response after at least 2 lines of therapy for recurrent or progressive CLL. (medscape.com)
While ibrutinib has been a clinical success, there are a subset of CLL patients who develop resistance to this therapeutic. (championsoncology.com)
The biochemical properties of acalabrutinib make it a suitable option for patients with treatment naïve CLL. (championsoncology.com)
patients impartial of Rai stage.3 Thus ZAP-70 Dimebon dihydrochloride is a rationale target for therapy in CLL. (sciencepop.org)
Loss of protective proteins on the cell surface makes the red blood cells of PNH patients sensitive to complement-mediated lysis. (sciencepop.org)
Accordingly, 44 CLL patients were included in the study, and among them 9 presented a del(17p). (bmj.com)
In my first paper, we describe the entire antibody discovery process where we developed antibodies capable of depleting chronic lymphocytic leukemia (CLL) cells using primary cells obtained from patients. (lu.se)

Ibrutinib is taken to decrease the size of lymph nodes, decrease the size of an enlarged liver or spleen, or to increase the number of good cells made in the bone marrow. (chemoexperts.com)
Ibrutinib is commonly taken to control symptoms from CLL or prevent CLL from progressing (getting worse). (chemoexperts.com)
When ibrutinib is taken alone, it may cause lymphocytosis , which is a rise in the white blood cell (WBC) count. (chemoexperts.com)
Ibrutinib covalently inhibits BTK, which is essential for B-cell homeostasis. (haematologica.org)
Ibrutinib is effective as a standalone treatment for mutated and unmutated CLL and when combined with rituximab is an effective therapy for relapsed CLL. (championsoncology.com)

We studied p53 phospho-profiles induced by DNA-damaging agents (fludarabine, doxorubicin) in 71 TP53-intact primary CLL samples. (muni.cz)
SCH900776 also increased the effect of fludarabine in a proportion of primary CLL samples treated with pro-proliferative stimuli, including those with TP53 disruption. (sch900776inhibitor.com)
We attempted to determine even more particularly the effect of different treatment routines on T-cell phenotype by further subgrouping the individuals into those who experienced received alemtuzumab and those who experienced received fludarabine/cyclophosphamide, since these medicines possess a known impact on Capital t cells.46,47 Desk 2. (rawveronica.com)
Chlorambucil (an alkylating agent) and fludarabine (a purine nucleoside analogue that acts as an antimetabolite) are commonly used in the treatment of chronic lymphocytic leukemia (chronic lymphoid leukemia, CLL). (medscape.com)
Purine analogues, fludarabine in particular, are very active against CLL. (medscape.com)
A nucleotide analogue of vidarabine, fludarabine is converted to 2-fluoro-ara-A, which enters the cell and is phosphorylated to form active metabolite 2-fluoro-ara-ATP, which inhibits DNA synthesis. (medscape.com)
It is indicated for CLL refractory to fludarabine and alemtuzumab, and also for previously untreated CLL in combination with chlorambucil. (medscape.com)

Understanding and targeting the mechanism of PI3Kδ-associated toxicity could allow us to more fully incorporate these agents into the CLL treatment paradigm and extend the duration of benefit from currently available therapies. (nature.com)
Here, we show that CIGB-300 promotes activation of the tumor suppressor PTEN and abrogates PI3K-mediated downstream signaling in CLL cells. (oncotarget.com)

It works by activating the immune system to destroy cancer cells. (medlineplus.gov)
This pre-clinical study provides important proof of concept that inducing inflammatory signaling in patient T-cells can successfully reshape the immune landscape of CLL tumors that sensitises them to the anti-tumour activity of immunotherapy. (kcl.ac.uk)
Bone marrow infiltration leads to a lack of healthy blood cells, thus leading to fatigue, susceptibility to bleedings and weakening of the immune system, exposing the patient to a higher risk of infection. (worldpharmanews.com)
In the early phases of cancer immune surveillance, NK cells directly identify and lyse cancer cells. (frontiersin.org)
instead of targeting tumor cells, the goal of immunotherapy is to augment and expand the immune system's intrinsic antitumor response. (frontiersin.org)
However, a class of important immune-modulators is conspicuously absent: agents that utilize the power of innate immune cells to eradicate tumors. (frontiersin.org)
An important class of innate immune cells that play a critical role in mediating the antitumor immune response is the natural killer (NK) cell. (frontiersin.org)
NK cells are now accepted to play an important role in both the adaptive and innate immune responses that govern infection, autoimmunity, and tumor immunosurveillance ( 2 , 3 ). (frontiersin.org)
Altogether, the results indicate that the crosstalk between Treg and neutrophils in CLL may play an important role in CLL progression by interfering with the immune response. (biomedcentral.com)
CB-012 is engineered with 5 edits, using our Cas12a chRDNA technology, which armor the CAR-T cells for improved antitumor activity through checkpoint disruption and immune cloaking. (cariboubio.com)
CB-012 is the first allogeneic CAR-T cell therapy, to Caribou's knowledge, with both checkpoint disruption, through a PD-1 knockout (KO), and immune cloaking, through a B2M KO and B2M-HLA-E fusion transgene insertion. (cariboubio.com)
Chronic lymphocytic leukemia (CLL) is characterized by an acquired immune dysfunction, which may underlie the hampered efficacy of cellular immunotherapy. (vu.nl)
Most data on dampened immune responses in CLL come from studies investigating CLL and T cell interactions. (vu.nl)
Medicinal and anatomical intraspecific biodiversity self-consciousness of the DCN-AGER axis guards against ferroptotic death-related intense pancreatitis as well as boundaries the ability of ferroptotic most cancers cells in order to induce any tumor-protective immune reaction. (sch900776inhibitor.com)
Chronic lymphocytic leukemia is normally characterized by reduced immune system functions largely credited to outstanding T-cell defects. (rawveronica.com)
Overview of the different T-cell subpopulations and Capital t cells conveying immune system checkpoints or service / expansion guns as likened between the different researched subject matter groupings. (rawveronica.com)
Novel understanding in the interaction between immune system and cancer cells of the patient holds great promise for immunotherapy development [ 4 - 6 ]. (hindawi.com)
However, from the beginning of puberty after thymus degeneration, human cytomegalovirus (HCMV) persists due to the chronic activation of cytomegalovirus in humans causing repeated activation of T cells, which is considered the driving factor of human immune aging [ 9 ]. (hindawi.com)
As these abnormal cells grow in excess, they disrupt normal cell production, which can result in a range of complications, particularly in the bones, blood, kidney and immune system. (lls.org)
For example, you have a cancer cell, and you want antibodies that can kill the cancer cell or activate a certain immune cell or so on, and then you develop the antibodies based on this. (lu.se)

It is also approved as a treatment for CLL that has recurred or is not responding to treatment with other drugs, with or without the immunotherapy rituximab (Rituxan). (cancercare.org)
D. Monocytes were found to decrease the density of surface-bound rituximab on CLL cells, a mechanism referred to as trogocytosis. (euromed2016.com)
Rituximab is a humanized murine monoclonal antibody against CD20, an antigen found on B-cells. (medscape.com)
Because CLL B-cells have low levels of CD20 expression, increased doses of rituximab may be necessary. (medscape.com)
Chronic lymphocytic leukemia (CLL) is the most common type of leukemia and the anti-CD20 monoclonal antibody, rituximab, represents the therapeutic gold standard for more than 2 decades in this pathology, when used in combination with chemotherapy. (bmj.com)

Alemtuzumab injection may cause a decrease in the number of blood cells made by your bone marrow. (medlineplus.gov)
CLL is a cancer that develops from overproduction of B cells in the bone marrow. (wikipedia.org)
The accumulation of functionally immature cells in the bone marrow excludes the generation of healthy cells and can become fatal. (worldpharmanews.com)
Each year in the United States, over 20,000 people are diagnosed with chronic lymphocytic leukemia (CLL), a cancer of the blood and bone marrow. (cancercare.org)
Lenalidomide (Revlimid) helps the bone marrow produce healthy blood cells while killing abnormal cells. (cancercare.org)

When overexpressed in CLL or in lymphomas or in malignancy, it is thought to export some tumor suppressor genes such as TP53 and therefore lead to their inactivation. (onclive.com)
Profile II samples were less capable of activating p53 target genes upon doxorubicin exposure, resembling TP53-mutant samples at the transcriptomic level, whereas standard p53 signaling was triggered in profile I. ATM locus defects were more common in profile II. (muni.cz)
Furthermore, the appearance degrees of 11 of 18 genes within this pathway had been moderately, yet regularly, elevated in the leukemia cells Calcipotriol of ROR1 TCL1 Tg mice in accordance with those of TCL1 mice (Fig. S5and Desk S2). (rawveronica.com)
Subnetwork analyses from the genes portrayed by ROR1 TCL1 leukemia cells versus TCL1 leukemia cells. (rawveronica.com)
A central adaptor protein of the noncanonical NF-κB pathway is NF-κB-inducing kinase (NIK), which activates the downstream kinase IKKα to process p100 to p52, thereby forming the RelB/p52 heterodimer to initiate the expression of target genes. (xiahepublishing.com)
As a key transcription factor of the Wnt/β-catenin pathway, LEF1 helps to regulate important genes involved in tumor cell death mechanisms. (oncotarget.com)
The viral transactivating protein p40Tax activates the genes for interleukin-2 (IL-2) and its receptor's high-affinity alpha chain. (medscape.com)

We are delighted to collaborate with Janssen's leading scientists to expand the scope of the plamotamab program, particularly as we explore opportunities to combine with novel B-cell targeted CD28 bispecific antibodies that can potentially selectively enhance T-cell cytotoxic activity," said Bassil Dahiyat, Ph.D., president and chief executive officer at Xencor. (pharmiweb.com)
Clinical relevance of this finding was shown by treatment with novel nanobody-Fc constructs, which induced cytotoxic responses in both CLL- and HC-derived NK cells via CD16. (vu.nl)
Reprogramming is a promising treatment, which redifferentiates T-induced pluripotent stem cells (T-IPSCs) into naïve and cytotoxic T cells or dedifferentiates within their own lineage [ 13 ]. (hindawi.com)

Targeted therapies focus on binding to specific molecules that are important for cancer cell survival and growth. (cancercare.org)
IL-4-dependent Jagged1 expression/processing is associated with survival of chronic lymphocytic leukemia cells but not with Notch activation. (unipg.it)
Notably, anti-Jagged1 antibodies partially prevented the IL-4-induced increase in Jagged1 processing and cell viability, suggesting that Jagged1 processing is one of the events contributing to IL-4-induced CLL cell survival. (unipg.it)
Consistent with this, Jagged1 silencing by small interfering RNA partially counteracted the capacity of IL-4 to promote CLL cell survival. (unipg.it)
So far, all accepted treatment regimens for CLL are neither curative nor associated with prolonged survival (1). (eotp.org)

The Syk family tyrosine kinase ZAP-70 is essential for normal T-cell development and signaling. (elsevierpure.com)
It does this by binding to and blocking the action of an enzyme within CLL cells known as Bruton's tyrosine kinase, otherwise known as BTK. (chemoexperts.com)

Immunotherapy is a type of cancer treatment that boosts the body's natural defenses to destroy cancer cells and has shown promise in treating several types of cancer. (kcl.ac.uk)
Immunotherapy that is based on antibodies which activate T-cells has revolutionised the area of cancer therapy. (kcl.ac.uk)
A team of researchers from the School of Cancer & Pharmaceutical Sciences, led by Dr. Alan Ramsay , reveal that the drug Avadomide can convert non responsive immunologically 'cold' CLL tumors into T-cell rich 'hot' ones, that can then effectively respond to immunotherapy antibodies. (kcl.ac.uk)
Natural killer (NK) cells may be an attractive alternative source of effector cells in immunotherapy in CLL, provided that functionality is retained within the CLL micro-environment. (vu.nl)
It is approved by the FDA as a first-line therapy for CLL, in combination with the immunotherapy obinutuzumab (Gazyva). (cancercare.org)

In individuals with CLL, higher levels of ZAP-70 is associated with a higher number of malignant B cells activated. (wikipedia.org)
In chronic lymphocytic leukemia, CD5+ B cells undergo malignant transformation. (msdmanuals.com)
Activation of CD40, expressed by normal as well as malignant B cells, is an important co-stimulatory signal that enhances cell viability and promotes isotype class switching [ 8 ]. (biomedcentral.com)
Virtually all MM cases begin as the pre-malignant plasma cell disorders monoclonal gammopathy of undetermined significance (MGUS) or smoldering multiple myeloma (SMM) and usually neither of them presents with symptoms. (lls.org)

This collaboration complements our plans to initiate combination clinical trials of plamotamab with tafasitamab and lenalidomide, and it expands our strategy to develop multiple highly active chemotherapy-free regimens for B-cell cancers. (pharmiweb.com)
There is compelling clinical and experimental evidence to suggest that natural killer (NK) cells play a critical role in the recognition and eradication of tumors. (frontiersin.org)
The preclinical data presented at AACR further support the clinical development of CB-012, Caribou's third program from our allogeneic CAR-T cell therapy platform," said Rachel Haurwitz, PhD, Caribou's president and chief executive officer. (cariboubio.com)
CIGB-300 is a cell-permeable selective CK2 inhibitor peptide undergoing clinical trials for several cancers. (oncotarget.com)
Of note, CD19, CD20, CD30, CD33, CD123, and CD269 as ideal targets have shown extraordinary potential for CAR-T cell therapy and other targets such as CD23 and SLAMF7 have brought promising future for clinical trials. (hindawi.com)
Although the clinical relevance of ZAP-70 in CLL is well known its molecular function is usually less comprehended. (sciencepop.org)

The samples also differed in the basal activity of the hypoxia pathway: the highest level was detected in TP53-mutant samples, followed by profile II and profile I. Our study suggests that wild-type TP53 CLL cells with less phosphorylated p53 show TP53-mutant-like behavior after DNA damage. (muni.cz)
Sjöberg A., Önnerfjord, P., Mörgelin, M., Heinegård, D. and Blom A. M. (2005) Extracellular matrix and inflammation: fibromodulin activates the classical pathway of complement by directly binding C1q. (lu.se)

PLCγ activates PKC via DAG, and this further phosphorylates downstream signaling proteins like ERK, p38 and ultimately leads to activation of the pleiotropic transcription factor NF-κB (p65) [ 5 ]. (biomedcentral.com)
CLL cells with both Un-and high ZAP-70 expression show increased activation of proteins downstream of the BCR such as Akt mitogen-activated protein kinase (MAPK) and NF-(7.0?compared with 8.3?compared with 6.0?with gefitinib and cell death was analyzed Dimebon dihydrochloride by flow cytometry after 24?h. (sciencepop.org)

Kinase proteins send signals to the cell's control center to help tumor cells grow. (cancercare.org)

The tandem SH2-domains of ZAP-70 are engaged by the doubly phosphorylated ITAMs of CD3-zeta, which positions ZAP-70 to phosphorylate the transmembrane protein linker for activation of T cells (LAT). (wikipedia.org)
[3] As antigen binds to the BCR, multiple protein tyrosine kinases are activated via interactions with the cytoplasmic domain of the BCR, including Lyn and Syk, as well as translocation of BTK to the plasma membrane through interactions with phosphatidylinositol-3,4,5 ( PIP3). (championsoncology.com)
Most of the MM CAR-T cell therapies that are under investigation are directed against the B-cell maturation antigen (BCMA) - a protein found on the surface of most myeloma cells. (lls.org)
Trouw L., Nilsson S., Goncalvez I., Landberg G. and Blom A. M. (2005) C4b-binding protein binds to necrotic cells and DNA, which limits DNA release and inhibits complement activation. (lu.se)

CIGB-300 demonstrated a dose-dependent antiproliferative and proapoptotic effect in a variety of tumor cells [ 20 ]. (oncotarget.com)
CAR-T therapy involves genetically engineering the patient's own T-cells to recognize and kill the patient's tumor cells. (lls.org)
GEP analyses were performed on highly purified, flow-cytometry sorted tumor-cells from eight subgroups of BCLs. (lu.se)

Owing to the prognostic value of B-CLL ZAP-70 expression, this phenotype may reflect intrinsic biological differences between the two subsets of disease. (elsevierpure.com)

B-lineage acute lymphoblastic leukemia (B-ALL) is the most common type of childhood cancer and mostly derives from immature B cells that carry the cell surface antigen CD19 (ref. 1 ). (nature.com)
Antigen stimulation via BCR in normal B cells initiates phosphorylation of the immunoreceptor tyrosine-based activation motifs (ITAMs) in the cytoplasmic tails of CD79a and CD79b. (biomedcentral.com)
E. NK cell-mediated ADCC of CLL cells previously exposed to monocytes, and thus allowing for antigen removal by trogocytosis, was lowered in 7 out of 8 performed experiments. (euromed2016.com)
Alemtuzumab is a humanized monoclonal antibody against CD52, an antigen found on B-cells, T-cells, and almost all CLL cells. (medscape.com)

Therapeutic intervention aims to reverse tumor-induced NK cell suppression and sustain NK cells' tumorlytic capacities. (frontiersin.org)
Chronic lymphocytic leukemia (CLL) remains an incurable malignancy, urging for the identification of new molecular targets for therapeutic intervention. (oncotarget.com)
Combined with other chemotherapeutic drugs, EA may be a promising therapeutic agent for CLL. (oncotarget.com)
Thus, improving the risk-stratification system for CLL and investigating more effective therapeutic agents are great challenges for the future management of CLL. (oncotarget.com)
B-cell lymphomas (BCLs) constitute a diverse set of tially identify new functional, diagnostic, and therapeutic tumors, both morphologically and clinically, that are mainly targets. (lu.se)

Subsequently, TAK1 activates the IKK complex and mediates IκBα phosphorylation and ubiquitin (Ub)-dependent proteasomal degradation, leading to the rapid and transient nuclear translocation of the classical NF-κB dimers. (xiahepublishing.com)

We found that Jagged1 was constitutively processed in CLL cells and generated an intracellular fragment that translocated into the nucleus, and an extracellular fragment released into the culture supernatant. (unipg.it)

Despite recent advances, chronic lymphocytic leukemia (CLL) remains incurable. (nature.com)
Despite significant improvements in treatment outcome in recent years [ 1 , 2 ], chronic lymphocytic leukemia (CLL) - the most common leukemia in the Western world - remains incurable [ 3 , 4 ]. (oncotarget.com)
CLL is highly heterogeneous in clinic and remains incurable at present. (oncotarget.com)

Changes in glycan structures and the interactions of these structures with endogenous carbohydrate- binding proteins, known as lectins, are now considered to be potential biomarkers on cancer cells for monitoring tu- mor progression. (fdocuments.net)
Indeed, blocking Notch-Jagged1 interactions among CLL cells with Jagged1 neutralizing antibodies did not affect the expression of the Notch target Hes1. (unipg.it)
As cells traffic through these microenvironments dynamic cell-cell interactions occur between mobile cells and tissue-resident cells. (sciencepop.org)
In particular gefitinib may have an effect in the lymph node microenvironments where BCR signaling occurs27 and ZAP-70 expression is usually upregulated.28 It is important to note that this complexity of feedback loops and interactions of ZAP-70 in CLL cells are not clearly understood making it difficult to definitively determine the precise action of gefitinib. (sciencepop.org)

Purine analogs are "antimetabolites" that interfere with DNA production and halt the growth of cancer cells. (cancercare.org)

Thus, further understanding of CLL biology and pathophysiology are mandatory for the identification of new molecular targets and the development of rational, more efficient therapies against this malignancy. (oncotarget.com)
Some localized melanomas may result from azathioprine, which acts synergistically with ultraviolet radiation, while T-cell depleting induction therapies may promote late stage tumors. (cdc.gov)

The B cells become continuously activated by acquisition of mutations that lead to monoclonal B-cell lymphocytosis (MBL). (msdmanuals.com)

For our in vivo and ex vivo experiments, we inoculated wild-type mice with TCL1 leukemic cells isolated from Eµ-TCL1 transgenic mice and then monitored disease progression by detecting leukemic cells in peripheral blood. (biomedcentral.com)
In this study, we investigated the effect of VPA on CLL cells ex vivo. (eotp.org)

Further, Xencor will apply its XmAb bispecific Fc technology to create and characterize XmAb CD28 bispecific antibody candidates against B-cell targets during a two-year joint research collaboration, and Janssen will have an exclusive worldwide license to develop selected molecules in combination with plamotamab and other agents, such as CD3 bispecific antibodies. (pharmiweb.com)
The defining functional feature of NK cells remains their intrinsic ability to conduct "natural killing" of cellular targets without prior sensitization. (frontiersin.org)
CIGB-300 is a cell-permeable peptide that modulates CK2 activity by binding to the phosphoacceptor site on CK2 targets [ 18 ]. (oncotarget.com)
They work by recognizing and finding specific proteins or targets on cancer cells. (lu.se)

The obtained results underline the plasticity of the neutrophil phenotype, observed under the influence of leukemic cells alone and depending on the presence of Treg. (biomedcentral.com)
Open in a separate window Physique 2 Monocytes restricted NK cell ADCC against autologous leukemic cells by production of ROSA. (euromed2016.com)

Results: We have evaluated TGR-1202 in 15 CLL lymphocyte samples, 10 with normal non-17pdel cytogenetics, and 5 with 17pdel. (duke.edu)

Efforts at using NK cells as antitumor agents began over two decades ago, but recent advances in elucidating NK cell biology have accelerated the development of NK cell-targeting therapeutics. (frontiersin.org)
We learned how imaging studies like MRIs can give us significant information about the biology of myeloma cells in addition to the flow cytometry tests. (healthtree.org)
These results provide new insight into normal human B-cell biology as well as provide clues about the transformed cell in B-CLL. (elsevierpure.com)
Despite increasing knowledge of the impact of Notch alterations on CLL biology and pathogenesis, the role of Jagged1 expressed in CLL cells remains undefined. (unipg.it)

Neither HDC nor catalase affected CLL cell viability or ADCC by NK cells in the absence of monocytes (data not shown). (euromed2016.com)

In January 2023, the FDA and EMA approved an additional second-generation irreversible BTK inhibitor, zanubrutinib, for CLL. (championsoncology.com)

These findings indicate that NK cells in CLL are not intrinsically defect and still perform effector functions upon adequate activating signaling. (vu.nl)
In contrast, anti-BCR induced signaling was highly impaired in SLL/CLL and MZL B cells as determined by low p-SFK, p-SYK and p-PLCγ levels. (biomedcentral.com)
In other cell types, it has been shown that after Notch engagement, Jagged1 not only activates Notch in signal-receiving cell, but also undergoes proteolytic activation in signal-sending cell, triggering a signaling with biological effects. (unipg.it)
ARQ-531 is a non-selective BTK inhibitor that suppresses signaling in cells with C481S BTK and PLCγ mutations. (championsoncology.com)
LOXO-305 inhibits signaling in cells with wild-type or C481S-mutated BTK. (championsoncology.com)
The signaling mechanisms of IL-21 in different cell types have been identified. (intechopen.com)
However, we know less about the biological effects of IL-21 and its signaling mechanisms in leukemia cells and monocytes. (intechopen.com)

In this study, highly purified, flow-cytometry sorted, classified in relation to normal B-cell differentiation [1]. (lu.se)

It is indicated for previously untreated CLL in combination with chlorambucil. (medscape.com)

MabCampath works in an entirely different way than chemotherapy, and is the first and only monoclonal antibody approved in Europe for the treatment of B-CLL, the leading form of adult leukemia in the Western hemisphere. (worldpharmanews.com)
To address the impact of this inhibitory mechanism, we exposed CD20 mAb-opsonized CLL cells to monocytes and ITGAV decided the level of bound antibody on CLL cells after 45 minutes of incubation. (euromed2016.com)
To investigate whether this reduction of bound antibody could explain the incomplete restoration of ADCC by antioxidative brokers, we removed monocytes from the CLL cells using anti-CD14 beads, re-introduced RTX (10g/ml) and decided the CLL susceptibility to ADCC. (euromed2016.com)
Ofatumumab is an anti-CD20 human monoclonal antibody that inhibits B-cell activation in early stages. (medscape.com)
Obinutuzumab is a CD20-directed cytolytic antibody, which, upon binding to CD20, mediates B-cell lysis. (medscape.com)
In PCH, the red blood cells are targeted by an autoantibody, the Donath-Landsteiner antibody, whose formation is most often triggered by infectious disease or neoplasms. (medscape.com)
This antibody attached to red blood cells (RBCs) in the cold and induced hemolysis when the RBCs are warmed due to complement activity. (medscape.com)
Intravascular hemolysis occurs preferentially at 37°C, at which temperature the antibody activates the classical complement cascade, providing the biphasic nature of the disease of D-L antibody binding at cold temperatures and hemolysis at wamer temperatures. (medscape.com)

The molecular features underpinning CAR-T cell persistence in our study remain unknown. (nature.com)
We systematically studied molecular features and clonal dynamics of CAR-T cells in children enrolled in the CARPALL study at serial timepoints, from production to persistence, up to 5 years after infusion. (nature.com)

As previously reported, chronic lymphocytic leukemia (CLL) cells show constitutive Notch1/2 activation and express the Notch ligand Jagged1. (unipg.it)

Such expansions of Compact disc5+B220low B cells resulted in advancement of clonal leukemia in each pet (Fig. S2), leading to lymphocytosis and splenomegaly resembling individual CLL, as assessed on necropsy (Fig. S4). (rawveronica.com)

This can be in comparison to earlier data centered on cytokine creation, displaying improved release of IL-4 in CLL, recommended to become credited to a Th2 polarization during disease development.25,43,44 We observed that previously treated modern individuals got significantly smaller amounts of all three subsets. (rawveronica.com)

Chemotherapy drugs, given intravenously (through a needle into a vein) or in pill form, can kill cancer cells. (cancercare.org)
Chemotherapy has long been an effective treatment for CLL, and is still considered in specific circumstances. (cancercare.org)
These 3 chemotherapy drugs, as well as oral azacitidine, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. (uci.edu)
Chemotherapy plus stem cell transplant has also been the standard treatment. (lls.org)

The data that supported this label expansion add to a growing body of evidence about the effectiveness of MabCampath as a single-agent treatment for B-CLL," stated Mark Enyedy, president of Genzyme Corporations's oncology business unit. (worldpharmanews.com)
In September, the United States Food and Drug Administration approved a supplemental Biologics License Application (sBLA) for alemtuzumab (trademarked as Campath in the U.S.) and granted regular approval for single-agent Campath for the treatment of B-cell chronic lymphocytic leukemia (B-CLL). (worldpharmanews.com)
Treatment of CLL doesn't always occur at diagnosis. (cancercare.org)
People with early-stage CLL who are not exhibiting symptoms typically don't receive treatment. (cancercare.org)
Treatment usually occurs if symptoms develop, if there is a decrease in the red blood cell count or platelet count, or if there is enlargement of the lymph nodes or spleen. (cancercare.org)
Both of these medications are approved by the U.S. Food and Drug Administration (FDA) as a first-line (initial) or subsequent treatment for CLL. (cancercare.org)
CLL therefore presents unique challenges to the development of new treatment strategies. (eotp.org)
Therefore, the implementation of novel, highly selective, and less toxic agents gains more and more importance in the treatment of CLL. (eotp.org)
Used collectively, our outcomes recommend that disease activity and earlier 501925-31-1 treatment possess a different effect on T-cell profile in CLL. (rawveronica.com)
Nevertheless, PD-1 and CTLA-4 phrase in modern disease had been therefore high that it can be fair to believe that these cells possess seriously damaged resistant features, as also recommended by previously released data.30,32 CLL treatment also appeared to dramatically impact T cells, in particular the CD4+ subset, in which a reduce of all T-helper subsets (Th1, Th2, Th17) was observed. (rawveronica.com)
Biologic agents are increasingly used in the treatment of CLL, typically in combination with chemotherapeutic agents. (medscape.com)

Aberrant activation of lymphoid enhancer-binding factor-1 (LEF1) has been identified in several cancers, including chronic lymphocytic leukemia (CLL). (oncotarget.com)
Lymphoid enhancer binding factor-1 (LEF1) is a member of the LEF/T-cell factor (TCF) family. (oncotarget.com)
Expression of galectins in normal lymphoid cells Each member of the galectin family exhibits a specific expression pattern in distinct tissues, and galectin expression is regulated during development. (fdocuments.net)

Since regulatory T cells (Treg) play an important role in CLL progression and influence the activity of neutrophils, we investigated the crosstalk between Treg and neutrophils in the spleen using a murine model of CLL. (biomedcentral.com)
This finding potentially suggests that ZMP may hypothetically allosterically activate GP, potentially leading to glycogenolysis in the intact murine model heart. (biotechpeptides.com)

Anatomy19

Organisms1

Diseases13

Chemicals and Drugs77

Analytical, Diagnostic and Therapeutic Techniques and Equipment20

Phenomena and Processes40

Health Care2

Associated with chr1

Lymphocytes27

Apoptosis19

Proliferation11

Microenvironment7

Cytotoxicity8

Malignancies18

Inhibitors11

Chronic lymphocyt1

Pathways16

Receptor19

Vitro4

Receptors7

Lymphoma17

Patients44

Ibrutinib5

Fludarabine7

PI3K2

Immune20

Rituximab5

Bone marrow5

Genes7

Cytotoxic3

Survival5

Tyrosine kinase2

Immunotherapy5

Malignant4

Clinical6

Pathway2

Downstream2

Kinase1

Protein4

Tumor cells3

Prognostic1

Antigen4

Therapeutic5

Phosphorylation1

Constitutively1

Remains incurable3

Interactions4

Purine1

Therapies2

Monoclonal B-cell lymphocytosis1

Vivo2

Targets4

Leukemic cells2

Lymphocyte1

Biology4

Viability1

20231

Signaling7

Flow cytometry1

Previously untreated1

Antibody8

Molecular2

Constitutive1

Lymphocytosis1

Cytokine1

Chemotherapy4

Treatment11

Lymphoid3

Murine model2