Resistance leukemia lymphocytic chronic b cell. Medical search. Frequent questions

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)
Chimeric antigen receptor-modified T (CAR T) cells exhibit very effective function in elimination of relapsed/refractory B-cell lymphoid malignancies, we investigated their use in a patient with relapsed MCL. (bmj.com)
B cell receptors (BCR) of mature lymphoid malignancies are exceptional in that they harbor tumor -specific-stereotyped sequences in the form of point mutations that drive self -engagement of the BCR and autologous signaling. (bvsalud.org)
Adoptive switch of allogeneic pure killer (NK) cells is changing into a reputable immunotherapy for hematological malignancies. (nfkb-p65.info)
Aberrant NFAT signaling is causally involved in the development of chronic lymphocytic leukemia, non-Hodgkin lymphoma, pancreatic cancer, and several other malignancies. (biomedcentral.com)
CD19-targeted CAR T cells therapy has shown remarkable efficacy in treatment of B cell malignancies. (biomedcentral.com)
Virtually absent from normal pediatric and adult tissues, with the exception of low-level expression in a subset of immature b cell precursors known as hematogones and adipocytes, ROR1 is notably overexpressed, and considered a survival factor, in a number of B lymphoid and epithelial malignancies: including chronic lymphocytic leukemia (CLL), mantle cell lymphoma (MCL), acute lymphoblastic leukemia (ALL), marginal zone lymphoma, lung adenocarcinoma. (peprotech.com)
PI3Kδ signaling pathways are frequently hyperactive in B-cell malignancies, making inhibition of PI3Kδ a promising target. (esmo.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)
So one possible option to keep the chronic lymphocytic leukemia/small lymphocytic lymphoma under control is to block another of the anti-death proteins, in this case, MCL1, with the preclinical, experimental molecule AZD5991. (cllsociety.org)
Targeting the B-cell receptor pathway with covalent, irreversible inhibitors of Bruton's tyrosine kinase (BTK) is integral to current treatment of chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL), although resistance often develops due to mutation of C481 in the BTK binding site. (universimed.com)
Indolent cases constitute approximately one third of all patient with non-Hodgkin's lymphoma and include follicular lymphoma, small lymphocytic lymphoma, marginal-zone lymphoma, and lymphoplasmacytic lymphoma with or without Waldenström's macroglobulinemia. (esmo.org)
Subtypes of indolent non-Hodgkin's lymphoma included follicular lymphoma (72 patients), small lymphocytic lymphoma (28), marginal-zone lymphoma (15), and lymphoplasmacytic lymphoma with or without Waldenström's macroglobulinemia (10). (esmo.org)

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)
MCL can be both indolent or aggressive, in either case it responds poorly to chemotherapy and consequently the aggressive form has a dismal prognosis assessed by incorporating Ki-67 proliferation index and Mantle Cell International Prognostic Index scores. (bmj.com)
miR‑223 and/or PAX6 were overexpressed and knocked down in U251 and U118 cells, and the half maximal inhibitory concentration (IC50) of TMZ and cell proliferation under TMZ treatment were used as measures of TMZ chemoresistance. (spandidos-publications.com)
The results demonstrated that overexpression of miR-223 in GBM cells markedly decreased TMZ-induced inhibition of cell proliferation and increased TMZ IC50, which could be abolished by overexpression of PAX6. (spandidos-publications.com)
On the other hand, knocking down miR‑223 in GBM cells with antagomir significantly enhanced the inhibitory effect of TMZ on GBM cell proliferation and decreased the TMZ IC50, which could be abolished by knockdown of PAX6. (spandidos-publications.com)
In conclusion, the present study demonstrated that TMZ inhibits GBM cell proliferation by inhibiting the expression of miR‑223, which leads to increased expression of tumor suppressor PAX6. (spandidos-publications.com)
The present study aimed to investigate the potential interaction among TMZ, PAX6 and miRNAs in GBM cells and assess its impact on GBM cell proliferation for, to the best of our knowledge, the first time. (spandidos-publications.com)
FLT3 ITD triggers the proliferation of the quiescent hematopoietic stem cell (HSC) pool but fails to directly transform HSCs. (biomedcentral.com)
CAR recognizes tumor-associated antigen targets and activates intracellular signals that stimulate proliferation of T cells, which identify and kill tumor cells. (biomedcentral.com)
GSK-3β helps maintain malignant cell survival and proliferation, particularly in terms of mediating resistance to standard anti-cancer therapies, through the NF-κB pathway. (outcomes4me.com)
Wnt-5a has since been suggested as a candidate ligand for ROR1, and ROR1 has been implicated to function as a pseudokinase, promoting proliferation and resistance to apoptosis in cancer cells through interaction with Wnt-5a, and TCL1-co-activation of AKT. (peprotech.com)
Bloom syndrome patients also demonstrate impairment in lymphocytic proliferation, deficient immunoglobulin synthesis, and lowered response to mitogen stimulation, resulting in impairment of both cellular and humoral immune responses. (medscape.com)

The mutations associated with PLAID are classified as germline, which means they are present in essentially all of the body's cells. (medlineplus.gov)
Several PLCG2 gene mutations have been associated with ibrutinib resistance, which is a condition in which the drug ibrutinib becomes ineffective in people with these mutations. (medlineplus.gov)
Using this grant, she identified mutations in the splicing factor SF3B1 connected to the development of chronic lymphocytic leukaemia (CLL). (wikipedia.org)
We employed longitudinal whole-exome sequencing on 2 patients whose disease progressed on pirtobrutinib and identified selection of alternative-site BTK mutations, providing clinical evidence that secondary BTK mutations lead to resistance to noncovalent BTKis. (lu.se)
Pirtobrutinib overcomes the C481 mutation via an alternative BTK binding mechanism, although other BTK mutations may evolve that mediate pirtobrutinib resistance. (universimed.com)
The concept of precision cell therapy targeting tumor -specific mutations is appealing but requires surface-exposed neoepitopes, which is a rarity in cancer . (bvsalud.org)
These data provide the basis for advanced approaches of resistance-preventive and biomarker -guided cellular targeting of functionally relevant lymphoma driver mutations sparing normal B cells . (bvsalud.org)
Gain-of-function PLCG2 mutations allow BTK-independent B-cell receptor signaling. (aacrjournals.org)
Strikingly, 5 of 6 patients had acquired a C481S mutation in BTK affecting the residue to which ibrutinib binds, and 2 patients had distinct mutations in phospholipase C gamma 2 ( PLCG2 ), which encodes a kinase that acts immediately downstream of BTK in the B-cell receptor (BCR) signaling pathway. (aacrjournals.org)
CD5+ DLBCL was associated with higher frequencies of >1 ECOG performance status, bone marrow involvement, central nervous system relapse, activated B-cell-like subtype, Bcl-2 overexpression, and STAT3 and NF-?B activation, whereas rarely expressed single-stranded DNA-binding protein 2 (SSBP2), CD30 or had MYC mutations. (unican.es)
They found that while tumor cells with certain gene mutations became more abundant after treatment, no mutation or group of mutations stood out as a cause of resistance. (cancerhealth.com)
BML mutations thus result in defects in DNA repair and genomic instability in the somatic cells, predisposing the patients to cancer development. (medscape.com)

BCL2, which is part of the p53 signaling pathway and regulates a form of cell death called apoptosis, is overexpressed in many patients with CLL. (blogspot.com)
The B cell receptor signaling pathway is a novel area of focus for investigational therapies in CLL. (medicalmvp.com)
To clarify mechanisms of salivary gland dysfunction, we identified a signaling pathway involved in the dedifferentiation of primary cultures of parotid acinar cells. (sykinhibitors.com)

Furthermore, co-treatment of KFr13Tx cells with MET inhibitors sensitized the tumor cells to PTX both in vitro and in vivo . (nature.com)
These results suggest that MET inhibitors administered concurrently with PTX could prevent the development of resistance to PTX. (nature.com)
Furthermore, the emergence of resistance ing surveillance of such resistance and further research on to neuraminidase inhibitors may limit the utility of prophy- optimal antiviral therapy in the immunocompromised. (cdc.gov)
The management of patients with chronic lymphocytic leukemia and mantle cell lymphoma who are treated with BTK inhibitors comes with intolerance and resistance challenges and therefore there is a continuous unmet need for novel treatments. (lls.org)
With that in mind, this Clinical Advances in BTK Inhibitors for Chronic Lymphocytic Leukemia and Mantle Cell Lymphoma was created to provide a broad range of educational activities on ongoing therapeutic developments in a variety of program formats to appeal to your individual learning preferences. (lls.org)
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)
Covalent inhibitors of Bruton tyrosine kinase (BTK) have transformed the therapy of chronic lymphocytic leukemia (CLL), but continuous therapy has been complicated by the development of resistance. (lu.se)
The most common resistance mechanism in patients whose disease progresses on covalent BTK inhibitors (BTKis) is a mutation in the BTK 481 cysteine residue to which the inhibitors bind covalently. (lu.se)
PGP inhibitors are being developed to overcome multidrug resistance and two that have reached clinical trials are varapamil, a calcium channel blocker, and cyclosporin A, an immunosuppressant [7]. (savedelicious.com)

The non-covalent BTK inhibitor pirtobrutinib provided a high response rate in patients with relapsed/refractory chronic lymphocytic leukemia previously treated with a covalent BTK inhibitor. (universimed.com)
The irreversible Bruton tyrosine kinase (BTK) inhibitor ibrutinib has shown significant clinical activity in patients with relapsed and refractory chronic lymphocytic leukemia (CLL), with over half of treated patients experiencing a complete or partial response. (aacrjournals.org)
This Phase 2, open-label, single-arm safety and efficacy study is evaluating GS-9973 (800 mg twice daily) in patients with relapsed or refractory CLL or NHL, including indolent NHL (iNHL), diffuse large B-cell lymphoma and mantle cell lymphoma. (medicalmvp.com)

Chimeric antigen receptor T (CART) cell therapy targeting the B cell specific differentiation antigen CD19 has shown clinical efficacy in a subset of relapsed/refractory (r/r) diffuse large B cell lymphoma (DLBCL) patients. (frontiersin.org)
Alemtuzumab is a humanized monoclonal antibody against CD52, an antigen found on B-cells, T-cells, and almost all CLL cells. (medscape.com)
Rituximab is a humanized murine monoclonal antibody against CD20, an antigen found on B-cells. (medscape.com)
The CD20 antigen is expressed on the surface of pre-B cells and mature B lymphocytes. (medscape.com)
BTK is a signaling molecule of the B-cell antigen receptor (BCR) and cytokine receptor pathways. (medscape.com)
Here, we use a BCR light chain neoepitope defined by a characteristic point mutation (IGLV3-21R110) for selective targeting of a poor- risk subset of chronic lymphocytic leukemia (CLL) with chimeric antigen receptor ( CAR ) T cells . (bvsalud.org)
FOXO1 overexpression in CAR T cells dramatically enhanced functionality in vitro and in vivo , especially in models of chronic antigen stimulation, and promoted a memory-like phenotype via flow cytometry, RNA-seq, and ATAC-seq. (bmj.com)
Chimeric antigen receptor T cell (CAR-T cell) therapy is a relatively new, effective, and rapidly evolving therapeutic for adoptive immunotherapies. (biomedcentral.com)
After encountering the antigen, Tn cells become activated and differentiat into Teff cells. (biomedcentral.com)
When the antigen is cleared, most Teffs undergo apoptosis and a small number of them differentiate into memory T cells. (biomedcentral.com)
However, relapse of primary disease remains a major obstacle after CAR T cells therapy, and the majority of relapses present a tumor phenotype with retention of target antigen (antigen-positive relapse), which highly correlate with poor CAR T cells persistence. (biomedcentral.com)
Disease relapse following CAR T cell therapy can be categorized into two major patterns: target antigen loss relapse or antigen-positive relapse. (biomedcentral.com)

However, ovarian cancers often acquire chemotherapeutic resistance to this agent. (nature.com)
6 Following the initial demonstration of the important role for miR in human cancer, such as downregulation of miR-15a-miR-16-1 in chronic lymphocytic leukemia, 7 a number of cancers have been shown to exhibit distinct miR expression patterns related to various phenotypes with remarkable cytogenetic abnormalities. (nature.com)
CLL treatment is often administered intermittently, and may also increase the risk of developing a second malignancy as skin and lung cancers, or other types of leukemia, lymphoma, and other cancers. (usc.edu)
Venetoclax is being studied as a treatment for other B-cell cancers, including diffuse large B-cell lymphoma (DLBCL), follicular lymphoma, and mantle cell lymphoma, Dr. Dunleavy added. (blogspot.com)
Aberrant overexpression of GSK-3β has been shown to promote tumor growth and chemotherapy resistance in various solid tumors including colon, ovarian, and pancreatic cancers and glioblastoma through differential effects on the pro-survival nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and c-Myc pathways as well on tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and p53-mediated apoptotic mechanisms. (outcomes4me.com)
By blocking a pro-survival protein called BCL-2 - which is especially abundant in many cancers - the drug causes tumor cells to heed the call of the pro-death proteins and do away with themselves through the process of apoptosis. (cancerhealth.com)
Since it was approved in 2016 for patients with a form of chronic lymphocytic leukemia (CLL), venetoclax has transformed the treatment of CLL and other blood-related cancers. (cancerhealth.com)
See Chronic Leukemias: 4 Cancers to Differentiate , a Critical Images slideshow, to help detect chronic leukemias and determine the specific type present. (medscape.com)

Dedicated to addressing the unmet needs of the chronic lymphocytic leukemia (CLL) and related blood cancer communities, we explain the rapidly changing therapeutic landscape and the importance of clinical trials, support and build patient networks, engage in research, and educate providers and patients. (cllsociety.org)
These unexpected findings open new therapeutic possibilities and support the notion that MdmX depletion is a critical mechanism for activating p53 signaling to control tumor cells," co-lead researcher Xinjiang Wang, PhD, said in a press release. (pharmacytimes.com)
Background CAR T cell therapy is a promising therapeutic modality for cancer treatment, but poor CAR T cell persistence limits efficacy in patients. (bmj.com)
1 CAR T cells with a memory-like phenotype are associated with durable persistence in patients and response to therapy, 2 thereby implicating memory as an important therapeutic axis. (bmj.com)
Myeloid immune cells, specifically tumor-associated macrophages (TAMs), may represent potential novel therapeutic targets in HCC, complementing current ablative or immune therapies. (cancerindex.org)

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)
The screening data suggested the involvement of other, less expected actors such as lymphoid transcription factors and central regulators of cellular energy metabolism - the process by which cells break down nutrients to power their activities. (cancerhealth.com)
When investigators took a census of the proteins in resistant lymphoid cells, they confirmed that many of the over- or underproduced ones arose from genes critical to energy metabolism. (cancerhealth.com)
Chronic lymphocytic leukemia (chronic lymphoid leukemia, CLL) is a monoclonal disorder characterized by a progressive accumulation of functionally incompetent lymphocytes (see the image below). (medscape.com)

Over the past ten years, the Longo lab demonstrated that periodic cycles of short-term fasting protect mice and possibly humans from the toxic side effects of chemotherapy, while increasing the chemotherapy's toxicity to a wide variety of malignant cells including breast cancer, melanoma, neuroblastoma, colorectal cancer and CLL. (usc.edu)

Understanding ibrutinib resistance mechanisms can guide efforts to treat or prevent resistant disease. (aacrjournals.org)
Although few ibrutinib-treated patients have relapsed to date, as the number of patients receiving ibrutinib increases it is crucial to characterize ibrutinib resistance mechanisms in order to devise treatment strategies for those who have relapsed and guide development of combination approaches to prevent resistance from developing. (aacrjournals.org)
instead, ibrutinib resistance can arise from a primary mutation in the target kinase or its immediate downstream target, neither of which are recurrently mutated in CLL. (aacrjournals.org)
Although additional ibrutinib resistance mechanisms likely remain to be discovered, this characterization of patients who have relapsed on ibrutinib may help initiate strategies to prevent or overcome ibrutinib resistance. (aacrjournals.org)

It blocks BCL-2 and allows a mass suicide of the CLL / SLL cells while sparing normal cells that have not distorted the apoptosis or cell death pathway. (cllsociety.org)
Pharmacologic Targeting MCL1 with AZD5991 Induces Apoptosis and Mitochondrial Dysfunction in Non-Hodgkin Lymphoma (NHL) Cells This is a complex and potentially significant topic, but Dr. Danilov makes it understandable. (cllsociety.org)
FL118 has previously been found to induce apoptosis by inhibiting the expression of cell-survival proteins. (pharmacytimes.com)
This agent binds CD20 on lymphocytes and induces apoptosis as well as initiating complement-mediated killing of bound cells. (medscape.com)
In many cases the antiproloferation action is caused by damage to DNA, which initiates apoptosis and cell death [4]. (savedelicious.com)

The complete remission rate (CR) in the treatment of recurrent/refractory B-cell acute lymphoblastic leukemia and B-cell lymphoma (R/R B-ALL)with CAR-T cell therapy is more than 90% and 50%, respectively [ 1 , 2 ]. (biomedcentral.com)

This activity is developed through a collaboration between The Leukemia & Lymphoma Society and Medscape Oncology. (lls.org)

Because CLL B-cells have low levels of CD20 expression, increased doses of rituximab may be necessary. (medscape.com)
Indolent B-cell non-Hodgkin lymphoma (NHL) that has progressed during or within six months of treatment with rituximab or a rituximab-containing regimen. (nih.gov)
Hence, with its novel mechanism of action and convenient oral once-daily regimen, venetoclax monotherapy or fixed 24-month combination therapy with rituximab represents an important option for treating RR CLL, including in patients with del(17p) or TP53 mutation and those failing a B cell receptor (BCR) inhibitor and/or chemotherapy. (sagepub.com)

She is a Professor of Medicine and Chief of Division of Stem Cell Transplantation and Cellular Therapies at the Dana-Farber Cancer Institute. (wikipedia.org)
The overall goal is to identify new drugs that will prevent or mitigate resistance to current lymphoma therapies. (seattlechildrens.org)
The patient received multiple molecularly targeted therapies, including targeting BTK and BCL2, and haplo-identical CAR T (haplo-CAR T) cells from her daughter without previous allo-hematopoietic stem cell transplantation. (bmj.com)
The Emerging Landscape of Immune Cell Therapies. (bmj.com)
Most patients with CLL eventually develop resistance to currently available therapies," said Jeff Sharman, MD, Willamette Valley Cancer Institute and Research Center - River Bend. (medicalmvp.com)

expressing high-risk chronic lymphocytic leukemia. (bvsalud.org)
Mutation-specific CAR T cells as precision therapy for IGLV3-21 R110 expressing high-risk chronic lymphocytic leukemia. (bvsalud.org)

Background The aggressive form of Mantle cell non-hodgkin B cell lymphoma (MCL) has a dismal prognosis. (bmj.com)
Mantle cell lymphoma (MCL) is a type of non-Hodgkin B cell lymphoma with a distinctive molecular marker cyclin D1 that is constitutively overexpressed in almost all cases. (bmj.com)

5 Although ovarian cancer in advanced stages initially appears to be chemotherapy sensitive as response rates to platinum-based therapy exceed 80%, long-term survival remains poor as a result of recurrence and emergence of drug resistance. (nature.com)
Case presentation Here, we report a case of a refractory MCL in a patient who had relapsed after conventional chemotherapy and autologous CAR T cell therapy. (bmj.com)
Presence of a heterogeneous population of cells with the possible varying degrees of resistance to chemotherapy was confirm by both methods. (cytgen.com)
CAR-T cell therapy is the fourth most common tumor treatment option after surgery, chemotherapy, and targeted therapy, and is successful in the treatment of malignant hematological tumors. (biomedcentral.com)
Resistance to chemotherapy is when the cancer cells do not respond to the drugs. (savedelicious.com)

In 2019, Wu continued her research on patients with chronic lymphocytic leukaemia and led a research study which collaborated with scientists at the Broad Institute, Massachusetts General Hospital, and the University of Washington. (wikipedia.org)
They found that genetic changes that occur very early in chronic lymphocytic leukaemia development directly influenced the growth pattern the CLL cells would ultimately take. (wikipedia.org)

The drug normally prevents a protein called BTK from sending signals for cells to grow and divide, which blocks the growth of cancer cells. (medlineplus.gov)
In understanding the background biology, CLL cells have learned how to increase or upregulate protein that keeps them alive. (cllsociety.org)
Venetoclax is the first FDA-approved drug that targets the BCL2 protein in cancer cells. (blogspot.com)
The protein encoded by this gene is a mitogen-inducible monokine and is one of the major HIV-suppressive factors produced by CD8+ T-cells. (cancerindex.org)
GS-9973 targets the Syk protein, which initiates most signaling from the B cell receptor. (medicalmvp.com)
GSK-3β is particularly important in tumor progression and modulation of oncogenes (including beta-catenin, cyclin D1 and c-Myc), cell cycle regulators (e.g. p27Kip1) and mediators of epithelial-mesenchymal transition (e.g. zinc finger protein SNAI1, Snail). (outcomes4me.com)
It's modes of action include downregulation of NF-κB and decreasing the expression NF-κB target genes including cyclin D1, Bcl-2, anti-apoptotic protein (XIAP) and B-cell lymphoma-extra large (Bcl-XL) leading to inhibition of tumor growth in multiple solid tumor cell and lymphoma lines and patient derived xenograft (PDX) models. (outcomes4me.com)
The combined data from these screens showed that resistant cells make too much MCL-1, a protein helps shore up the mitochondrial membrane. (cancerhealth.com)
But there was more to venetoclax resistance than the mischief made by a single overabundant protein. (cancerhealth.com)
Receptor-tyrosine-kinase-like orphan receptor 1 (ROR1) is a tumor-associated, surface protein predominantly expressed during embryogenesis, where it is involved in organ morphogenesis, nervous system development, and neural progenitor cell maintenance and survival. (peprotech.com)
BLM encodes 1417 amino acids that code for a protein in the nuclear matrix of growing cells, which is a member of the RecQ family of helicases. (medscape.com)

BCL2 overexpression is associated with increased drug resistance and tumor cell survival. (blogspot.com)

Pirtobrutinib after a covalent BTK inhibitor in chronic lymphocytic leukemia. (universimed.com)
Ablation of PI3K blocks BCR-ABL leukemogenesis in mice, and a dual PI3K/mTOR inhibitor prevents expansion of human BCR-ABL+ leukemia cells. (ucsf.edu)
FLT3 ITD /NFATC1-AML is re-transplantable in secondary recipients and shows primary resistance to the FLT3 ITD -kinase inhibitor quizartinib. (biomedcentral.com)
Venclexta®) is a first-in-class, oral, selective B cell lymphoma-2 (BCL-2) inhibitor. (sagepub.com)

To trace the source of venetoclax resistance, researchers led by Catherine J. Wu, MD , of Dana-Farber and the Broad Institute, and spearheaded by postdoctoral research fellow Romain Guièze MD, PhD, and Harvard Medical School student Vivian Liu, first used leukemia samples that had been collected from six patients before treatment with venetoclax and at the time of relapse. (cancerhealth.com)
Our work shows that venetoclax resistance involves alterations in the biology of the both inner and outer membranes of the mitochondria," Wu comments. (cancerhealth.com)

Compared to healthy controls (n=24), DLBCL patients (n=33) showed significant lymphopenia, due to low CD3 + CD4 + T helper and CD3 - CD56 + NK cell counts, while cytotoxic CD3 + CD8 + T cell counts were similar. (frontiersin.org)
In vitro , CD3 + CD8 + CD27 - CD28 - compared to CD3 + CD8 + CD27 + CD28 + CART cells displayed similar CD19 + target cell-specific cytotoxicity, but were hypoproliferative and produced less cytotoxic cytokines (IFN-γ and TNF-α). (frontiersin.org)

When foreign invaders are detected, the PLCγ2 enzyme relays signals for B cells to produce specialized proteins called antibodies (or immunoglobulins) that attach to foreign particles and mark them for destruction. (medlineplus.gov)
Fluorescent staining of actin filaments in fixed tissue sections and tissue culture cells preparations.Note: Unlike many actin antibodies, Acti-stain™ 555 phalloidin binds only to F-actin resulting in low background fluorescence. (cytoskeleton.com)
Antagonistic Human FcγRIIB (CD32B) Antibodies Have Anti-Tumor Activity and Overcome Resistance to Antibody Therapy In Vivo. (lu.se)

Diffuse large B cell lymphoma (DLBCL) represents the most frequent form of non-Hodgkin's lymphoma (NHL). (frontiersin.org)
Abstract: CD5 is a pan-T-cell surface marker and is rarely expressed in diffuse large B-cell lymphoma (DLBCL). (unican.es)
Age cutoff for Epstein-Barr virus-positive diffuse large B-cell lymphoma-is it necessary? (unican.es)

Obinutuzumab is a CD20-directed cytolytic antibody, which, upon binding to CD20, mediates B-cell lysis. (medscape.com)

FL118-based therapy may also be beneficial for a subgroup of cancer patients who have tumors in which MdmX overexpression causes treatment resistance, such as in chronic lymphocytic leukemia and melanomas. (pharmacytimes.com)
Here, we demonstrate that FOXO1 is required for the development of memory CAR T cells and that FOXO1 overexpression maintains memory gene expression programs and enhances CAR T cell antitumor activity in liquid and solid tumor models. (bmj.com)
A FOXO1 regulon consisting of 41 putative FOXO1 target genes, which were unbiasedly identified in our knockout and overexpression studies, highly correlated with long-term persistence and positive outcomes in patients treated with CD19 CAR T cells. (bmj.com)
Conclusions Our results demonstrate that FOXO1 is a master regulator of CAR T cell memory programming and that overexpression of FOXO1 triggers both transcriptional and epigenetic changes in CAR T cells that enhance memory differentiation, persistence, and potency. (bmj.com)
Overexpression of miR‑223 increases TMZ chemoresistance, while inhibition of miR‑223 with antagomir markedly decreases TMZ chemoresistance in GBM cells. (spandidos-publications.com)

We demonstrate that primary CLL cells from responding patients on the pirtobrutinib trial show reduced BCR signaling, cell survival, and CCL3/CCL4 chemokine secretion. (lu.se)
Therefore, study on factors and mechanisms that limit the in vivo persistence of CAR T cells is crucial for developing strategies to reduce the probability of tumor relapse and improve the long-term disease-free survival for patients who are treated with CAR T cells. (biomedcentral.com)
The mitochondria - where nutrients from food are converted into fuel for the cell - serve as a kind of jury box where pro-survival proteins contend with proteins that favor cell death. (cancerhealth.com)

Inhibition of PI3K δ induces disruption of interactions between malignant B cells and their microenvironment. (haematologica.org)
Along with ibrutinib, which targets Bruton's tyrosine kinase (BTK), idelalisib represents a new class of agents that target signal transduction downstream of the B-cell receptor (BCR) in malignant B cells. (esmo.org)

The overall result of the genomic instability in the proliferating cells is a high risk of malignancy, reduced fertility or infertility, B- and T-cell immunodeficiencies, and cutaneous manifestations, including photosensitivity, poikiloderma, and telangiectatic erythema. (medscape.com)

Gene- expression profiling demonstrated that B-cell receptor signaling dysfunction and microenvironment alterations are the important mechanisms underlying the clinical impact of CD5 expression. (unican.es)

We employ screening and targeted testing (CRISPR and small molecule) to ask which genes and pathways are required in B cells and primary lymphoma cells for resistance to lymphoma drugs. (seattlechildrens.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)
When patients develop resistance, multiple drugs with different pathways of entry and different cellular targets are used. (savedelicious.com)

A key reason for this is dysregulated tumor cell metabolism, which confers large amounts of metabolic interference to CAR-T cells, resulting in functional failure of CAR-T cell therapy. (biomedcentral.com)

Andreieva S.V., Korets K.V., Skorokhod I.M., Ruzhinska O.E. Cytogenetic and molecular cytogenetic investigations in relapse of B-cells chronic lymphocytic leukemia, Tsitol Genet. (cytgen.com)
In close collaboration with John Doench, PhD, associate director of the Genetic Perturbation Platform at the Broad, they embarked on a more wide-ranging probe of the cells' molecular changes. (cancerhealth.com)

At time of progression, these primary CLL cells show increasing resistance to pirtobrutinib in signaling inhibition, cell viability, and cytokine production. (lu.se)
MCL1 inhibition causes damage to the mitochondrial structure leading to rapid cell death. (cllsociety.org)

We are using mass spectrometry-based proteomics and sequencing to determine how signaling is altered in lymphoma cells from patients on therapy. (seattlechildrens.org)
Despite this heterogeneous response, blood pre-infusion biomarkers predicting responsiveness to CART cell therapy are currently understudied. (frontiersin.org)
Blood cell and serum markers, along with clinical data of DLBCL patients who were scheduled for CART cell therapy were evaluated to search for biomarkers predicting CART cell responsiveness. (frontiersin.org)
Conclusions This case suggests that haplo-CAR T cell therapy can be effective in controlling lymphoma that failed to respond to autologous CAR T cell therapy and overcome limitation of autologous CAR T cells, thus may be one possible regimen before the era of off-the-shelf "universal" CAR T cell therapy. (bmj.com)
The accelerated approval is for patients with CLL whose tumor cells are missing a portion of chromosome 17, commonly referred to as a 17p deletion, and who have received at least one prior therapy for their cancer. (blogspot.com)
Public datasets were reanalyzed to evaluate FOXO1 activity in patients treated with CAR T cell therapy. (bmj.com)
Our findings further demonstrate the potential for transcription factor engineering as an approach to generate highly effective CAR T cell products for antitumor therapy. (bmj.com)
Therefore, there is an urgent need to identify novel strategies for enhancing CAR-T cell therapy. (biomedcentral.com)
An abstract from the ASH annual meeting shows that during CAR-T cell manufacturing each stage has different functional and metabolic requirements and small changes can have large effects on the efficacy and side effects of CAR-T cell therapy [ 7 ] (Fig. 1 ). (biomedcentral.com)
However, ~ 30-50% of patients experienced leukemia relapse, the majority relapsed within 1 year after CAR T cells therapy [ 6 ], and with prolonged follow-up, the relapse rate may be much higher. (biomedcentral.com)
Venetoclax for patients with chronic lymphocytic leukemia who progressed during or after idelalisib therapy. (sagepub.com)

We found that miR-31 was downregulated in KFr13Tx cells, and that re-introduction of miR31 re-sensitized them to PTX both in vitro and in vivo . (nature.com)
Haplo-CAR T cells could effectively proliferate in vivo and had a clinically significant antitumor activity without serious side effects. (bmj.com)
In vivo experiments confirm epitope -selective cytolysis in xenograft models in female mice using engrafted IGLV3-21R110 expressing cell lines or primary CLL cells . (bvsalud.org)
Results FOXO1 knockout in human CAR T cells prevented the development of a memory-like phenotype, and instead, promoted an exhausted phenotype and gene expression profile and attenuated antitumor activity in vitro and in vivo . (bmj.com)
Furthermore, we summarize the latest developments and newest strategies to improve the metabolic adaptability and antitumor activity of CAR-T cells in vitro and in vivo. (biomedcentral.com)
In vitro expansion of T cells and CAR-T cells requires proper metabolism to maintain a undifferentiated state, which must extend through the in vivo use to enhance antitumor activity. (biomedcentral.com)
Additionally, we summarize the latest developments and newest strategies for improving the metabolic adaptability and antitumor activity of CAR-T cells in vitro and in vivo. (biomedcentral.com)
Therefore, study on factors and mechanisms that limit the in vivo persistence of CAR T cells is crucial for developing strategies to overcome these limitations. (biomedcentral.com)
In this review, we summarize the rapidly developing knowledge regarding the factors that influence CAR T cells in vivo persistence and the underlying mechanisms. (biomedcentral.com)
Various factors in the process contribute to impact the in vivo persistence and durable antitumor effects of CAR T cells. (biomedcentral.com)

Preliminary in vitro (test-tube) studies by our research team have already demonstrated 100% kill rate of CLL cells using a combination of specific FDA-approved agents and FMD. (usc.edu)
Our initial in vitro research using mouse CLL cells found that a combination of three common cancer drugs, which when given with dietary restriction, succeeded in killing 100% of the CLL cells. (usc.edu)
Using in vitro ibrutinib-resistant models and cells from patients with CLL, we show that pirtobrutinib potently inhibits BTK-mediated functions including B-cell receptor. (lu.se)
Using in vitro ibrutinib-resistant models and cells from patients with CLL, we show that pirtobrutinib potently inhibits BTK-mediated functions including B-cell receptor (BCR) signaling, cell viability, and CCL3/CCL4 chemokine production in both BTK wild-type and C481S mutant CLL cells. (lu.se)
CAR T cell function was assessed in vitro using tumor co-culture assays wherein cytokine secretion, killing, and metabolic fitness (via Seahorse) were measured. (bmj.com)
Targeting chronic lymphocytic leukemia cells in the tumor microenviroment: A review of the in vitro and clinical trials to date. (wjgnet.com)

Acute myeloid leukemia (AML) patients with a high allelic burden of an internal tandem duplication ( ITD )-mutated FMS - like Tyrosine Kinase - 3 ( FLT3 ) have a dismal outcome. (biomedcentral.com)
Acute myeloid leukemia (AML) is mainly a fatal disease. (biomedcentral.com)

Resistance mechanisms for the Bruton's tyrosine kinase inhbitor ibrutinib. (aacrjournals.org)
First identified during PCR-based cloning of a human neuroblastoma cell line in search of tyrosine kinases similar to tropomyosin-receptor-kinase (Trk) neurotropic receptors, ROR1, along with the related receptor tyrosine kinase (RTK) ROR2, was catalogued as an "orphan" receptor due to the fact its related ligand remained elusive. (peprotech.com)

Today, Glenn is not only alive, but a 2012 biopsy at Harvard confirmed that his bone marrow contains no leukemic cells. (scienceblogs.com)
Analysis of bone marrow cells chromosomal abnor-malities in relspse of 61 patients with B-cell chronic lymphocytic leukemia were performed. (cytgen.com)
CLL is a slow-growing cancer in which the bone marrow overproduces white blood cells, leaving less room in the blood and bone marrow for other types of blood cells. (medicalmvp.com)
Chromosomal aberrations (hypo- and hyperdiploidy, deletions, breaks, and gaps) in peripheral lymphocytes and bone marrow cells are the predominant effects seen in humans. (cdc.gov)

CRC develops in a progressive fashion during which normal colon epithelial cells transform to form benign growths such as polyps. (biomedcentral.com)

(C) Expressions of RNASET2 in 18 types of human blood cells and total peripheral blood mononuclear cells (PBMC) were analyzed in the Blood Atlas database. (frontiersin.org)

Half of the mice engrafted with bulk lymphocytes including CD4(+) T cells died before analysis probably due to xenoreactive graft versus host disease. (sykinhibitors.com)

To understand drug resistance in lymphoma, the James lab collects primary samples from subjects with lymphoma treated with ibrutinib and other targeted agents. (seattlechildrens.org)
Also the main mechanism of resistance to these drugs will be explored, particularly focusing on the role of P-glycoprotein and how it can be modulated to reverse drug resistance. (savedelicious.com)

The immune effector cell mechanisms include antibody-dependent cellular cytotoxicity and antibody-dependent cellular phagocytosis. (medscape.com)
In this review, we summarize the rapidly developing knowledge regarding the influence factors and mechanisms of poor CAR T cells persistence, and also the potential strategies to overcome these limitations. (biomedcentral.com)
However, cancer cells can become multidrug resistant, a phenomenon due to cells expressing mechanisms that cause simultaneous resistance to many different, structurally and functionally, unrelated drugs [6]. (savedelicious.com)

They thought that inefficient removal of peroxide might be responsible for the high rates of sister chromatid exchange and chromosomal damage in Bloom syndrome cells. (medscape.com)

We measure the effects of these variants on B cell differentiation, lymphoma initiation, and response to drugs. (seattlechildrens.org)
Inevitably, there are fundamental and applied questions, such as those relating to transcriptional control of stem cell differentiation, intrinsic noise in gene expression, and the origins of disease, that may only be addressed at the single cell level. (justia.com)
Of note, among these influence factors, CAR T cells differentiation and exhaustion are identified as the central part due to the fact that almost all factors eventually alter the state of cells differentiation and exhaustion. (biomedcentral.com)

The Leukemia & Lymphoma Society® (LLS) is a global leader in the fight against blood cancer. (lls.org)
The Leukemia & Lymphoma Society is a 501(c)(3) organization, and all monetary donations are tax deductible to the fullest extent allowed by tax laws. (lls.org)

CLL, the most common form of adult leukemia (or blood cancer) in the United States and European countries, results from the progressive clonal expansion of leukemic cells derived from normal lymphocytes. (usc.edu)

We further demonstrate in two humanized mouse models lack of cytotoxicity towards human B cells . (bvsalud.org)
As they demonstrate in a recent paper in Cancer Cell, the mechanism has two components, both of which involve mitochondria, the lozenge-shaped structures that provide energy for the cell. (cancerhealth.com)

Wu later led a study which uncovered why some patients become resistant to Venclexta, a Leukemia drug. (wikipedia.org)
The Food and Drug Administration (FDA) approved venetoclax (Venclexta®) on April 11 for patients with chronic lymphocytic leukemia (CLL) whose tumors have a specific genetic alteration. (blogspot.com)

Anatomy23

Organisms19

Diseases41

Chemicals and Drugs77

Analytical, Diagnostic and Therapeutic Techniques and Equipment29

Phenomena and Processes70

Anthropology, Education, Sociology and Social Phenomena1

Information Science3

Health Care1

Malignancies10

Small lymphocy5

Proliferation13

Mutations12

Signaling pathway3

Inhibitors10

Patients with relapsed3

Antigen12

Cancers8

Therapeutic5

Lymphoid4

Colorectal cancer1

Ibrutinib resistance4

Apoptosis5

Acute lymphobl1

Oncology1

Rituximab3

Therapies5

High-risk chronic lymphocy2

Mantle2

Chemotherapy5

Leukaemia2

Protein11

BCL21

Inhibitor4

Venetoclax resistance2

Cytotoxic2

Antibodies3

Diffuse large B3

Mediates1

Overexpression5

Survival3

Malignant B cells2

Genomic1

Microenvironment1

Pathways3

Tumor cell1

Molecular2

Inhibition2

Therapy11

Vivo10

Vitro6

Myeloid2

Tyrosine2

Bone4

Epithelial1

Peripheral blood mononuclear cells1

Graft Versus1

Drug resistance2

Mechanisms3

Chromosomal1

Differentiation3

Lymphoma Society2

Lymphocytes1

Demonstrate2

Venclexta2