Acute lymphoblastic leukemia (ALL) is the most common childhood malignancy. Most ALL cases originate from immature B-cells (BCP-ALL) and are characterized by reoccurring structural genetic aberrations. These aberrations hold information of the pathogenesis of ALL and are used for risk stratification in treatment. Despite increased knowledge of genetic aberrations in pediatric T-cell ALL (T-ALL), no reliable molecular genetic markers exist for identifying patients with higher risk of relapse. The lack of molecular prognostic markers is also evident in patients with relapsed ALL. During the last decades, aberrant epigenetic mechanisms including DNA methylation have emerged as important components in cancer development. Telomere maintenance is another important factor in malignant transformation and is crucial for long-term cell survival. Like DNA methylation, telomere length maintenance has also been implicated to reflect outcomes for patients with leukemia.. In this thesis, the prognostic ...
We have tested a panel of eight CCR7-function scAbs for their ability to block binding of CCR7 ligand binding, and downstream signaling events (Ca2+mobilization, transmigration), and have identified a subset that can block CCR7 activation, and receptor-mediated binding to ligand in vitro, with an EC50 of 1.89nM to 5.49nM. At a 1 µM concentration, our top 2 scAbs blocked calcium mobilization in Chem-1 CCR7 expressing cells. In the presence of the EC50 concentration for each antibody, we have identified a single candidate scAb that successfully blocked transmigration of primary human T-ALL across an HBEC monolayer. At present studies are ongoing to determine if these antibodies can prevent breech of the blood brain barrier in vivo. ...
Although it has been previously reported that bee venom can inhibit human cancer cell growth through induction of apoptosis in many cancer cell lines such as prostate cancer, breast cancer and melanoma, there is no finding of the induction of apoptosis in human T cell acute lymphoblastic leukemia cells by BV [6-8]. Based on our knowledge, the present study is the first report about examination of the synergistic effect of BV with a palladium metal-based component.. Analysis of cytotoxicity by MTT assay proved that BV is both time- and dose-dependent in its cytotoxic effects, given that the Cc50 values of this component were 6.3 and 0.6 μg/mL after 24 and 48 hours, respectively. Due to the inconsistency in the MTT assay data - as a result of precipitation of the BV at high concentrations after 24 and 48 hours, and at low concentrations after 48 hours - only the concentrations less than 10 μg/mL were applied in these experiments. At these concentrations the findings were acceptable, except at 8 ...
MicroRNAs (miRNAs) play important roles in the pathogenesis of many types of cancers by negatively regulating gene expression at posttranscriptional level. However, the role of microRNAs in leukaemia, particularly T-cell acute lymphoblastic leukaemia (T-ALL), has remained elusive. Here, we identified miR-664 and its predicted target gene PLP2 were differentially expressed in T-ALL using bioinformatics methods. In T-ALL cell lines, CCK-8 proliferation assay indicated that the cell proliferation was promoted by miR-664, while miR-664 inhibitor could significantly inhibited the proliferation. Moreover, migration and invasion assay showed that overexpression of miR-664 could significantly promoted the migration and invasion of T-ALL cells, whereas miR-664 inhibitor could reduce cell migration and invasion. luciferase assays confirmed that miR-664 directly bound to the 3untranslated region of PLP2, and western blotting showed that miR-664 suppressed the expression of PLP2 at the protein levels. This ...
The homeobox gene TLX1 (for T-cell leukemia homeobox 1, previously known as HOX11) is inappropriately expressed in a major subgroup of T cell acute lymphoblastic leukemia (T-ALL) where it is strongly associated with activating NOTCH1 mutations. Despite the recognition that these genetic lesions cooperate in leukemogenesis, there have been no mechanistic studies addressing how TLX1 and NOTCH1 functionally interact to promote the leukemic phenotype. Global gene expression profiling after downregulation of TLX1 and inhibition of the NOTCH pathway in ALL-SIL cells revealed that TLX1 synergistically regulated more than 60% of the NOTCH-responsive genes. Structure-function analysis demonstrated that TLX1 binding to Groucho-related TLE corepressors was necessary for maximal transcriptional regulation of the NOTCH-responsive genes tested, implicating TLX1 modulation of the NOTCH-TLE regulatory network. Comparison of the dataset to publicly available biological databases indicated that the TLX1/NOTCH-coregulated
In this study, we aimed to identify somatic structural variation of T-cell acute lymphoblastic leukemias (T-ALLs_ from patient-derived xenografts (PDX) at the single-cell level. For this purpose, we performed strand-specific single-cell sequencing of PDX-derived T-ALL relapse samples from two juvenile patients (P1, P33). To validate structural variation detected via scTRIP, we profiled whole exome sequencing (WES) data from P33 (samples taken during initial disease, remission, relapse), and mate-pair sequencing data from P1 (relapse). ...
In the present study, we have determined p16 deletion status using FISH analysis for a large group of childhood T-ALL cases at diagnosis, and examined the impact of homozygous p16 deletion on in vitro drug resistance and clinical outcome within this group.. The frequency of p16 deletions in this study, 68·4%, is in agreement with the published data (Hebert et al, 1994; Fizzotti et al, 1995; Ohnishi et al, 1995; Okuda et al, 1995; Diccianni et al, 1997). The majority of these deletions were homozygous, but 7% had hemizygous deletions, i.e. one allele detectable, and 14% presented a mixture of populations with 0-2 alleles. The detection of this latter group is a further refinement offered by the FISH technique. These hemizygous and mixed population groups are too small to be analysed as separate entities and are hence excluded from the data presented. One could also add these cases to the p16+/+ and/or p16−/- groups. It seems most logical to then place the hemizygously deleted cases in the ...
Background: Chromosomal translocations resulting in alternative fusions of the human TEL (ETV6) and JAK2 genes have been observed in cases of acute lymphoblastic leukemia and chronic myelogenous leukemia, but a full understanding of their role in disease etiology has remained elusive. This study investigated potential differences between these alternate TEL-JAK2 fusions, including their lineage specificity. Design and Methods: Both T-cell acute lymphoblastic leukemia and atypical chronic myelogenous leukemia derived TEL-JAK2 fusion types were generated using the corresponding zebrafish tel and jak2a genes and placed under the control of either the white blood cell-specific spi1 promoter or the ubiquitously-expressed cytomegalovirus promoter. These constructs were injected into zebrafish embryos and their effects on hematopoiesis examined using a range of molecular approaches. In addition, the functional properties of the alternate fusions were investigated in vitro. Results: Injection of the ...
Intimacy counselling. Find out more about our free, confidential counselling with medical specialists trained in intimacy, body image, sexual confidence and relationships. Available to all those facing cancer and their partners, including members of the LGBTQI community. ...
T-cell acute lymphoblastic leukemia (T-ALL) cells and thymocytes, their normal counterpart, undergo spontaneous apoptosis when cultured in vitro. Co-cultures with bone marrow (BM)1,2 or thymic stroma3 can induce T-ALL survival and proliferation. However, the molecular mechanisms promoting these effects in the microenvironments remain poorly elucidated. Interleukin-7 (IL-7), produced by BM and thymic stroma, plays a crucial role in the development of normal T cells4 and contributes to the pathogenesis of T-cell leukemia.5 IL-7 induces survival6 and proliferation of early thymocytes7 and regulates survival, cell cycle, and growth of primary T-ALL cells.5. To explore the mechanisms involved in the enhanced survival mediated by BM stroma, we cultured primary T-ALL cells or normal human thymocytes in vitro with either human BM stromal cells obtained from seven healthy donors, as previously described,8 or the murine M2-10B4 fibroblast-like cell line of BM stromal origin (kindly provided by Dr Connie J ...
GlaxoSmithKlines Atriance® (nelarabine solution for infusion) has received a positive opinion from the European Medicines Agency (EMEA) for the treatment of T-cell acute lymphoblastic leukaemia (T-ALL) and T-cell lymphoblastic lymphoma (T-LBL) in patients whose disease has not responded to, or has relapsed following, treatment with at least two chemotherapy regimens.. Atriance® is now being considered for final marketing approval by the European Commission for these difficult to treat forms of acute lymphoblastic leukaemia (ALL) and lymphoblastic lymphoma (LBL): T-ALL and T-LBL.. According to Paolo Paoletti, SVP and Global Head of Oncologylinks Research and Development, GSK:. "Nelarabine may offer some patients the chance to go on to have potentially curative treatment, such as a stem cell transplant, so we are delighted that nelarabine has been granted a positive opinion from the EMEA.. We are immensely proud of our involvement in the development of this orphan drug for such a rare disease, ...
The Notch signalling pathway is important in development and differentiation of a diverse range of both embryonic and adult tissues. There is now strong evidence implicating aberrant Notch signalling in the pathogenesis of T-cell acute lymphoblastic leukaemia (T-ALL), with over 50% of paediatric patients having activating mutations in NOTCH-1. This thesis aims to explore several aspects of the Notch pathway in both T-ALL and acute myeloid leukaemia (AML). Chapter one summarises the published data on the Notch signalling pathway itself, addressing the basic understanding of Notch activation through cell-to-cell interaction, as well as the mechanisms through which it is regulated. The role that Notch signaling plays in normal haematopoiesis is also discussed. Chapter three addresses the incidence and characteristics of NOTCH-1 mutations in a cohort of adult patients with T-ALL in comparison to the published study of paediatric T-ALL, as well as in a cohort of patients with infantile leukaemia and ...
About 13% to 15% of children with ALL have T-cell ALL. This type of leukemia affects boys more than girls, and generally affects children at an older age than B-cell ALL does. It is often associated with an enlarged thymus (which can sometimes cause breathing difficulty) and with early spread to the cerebrospinal fluid (the fluid that surrounds the brain and spinal cord).. ...
This information is intended for physicians and related personnel, who understand that medical information is often imperfect, and must be interpreted in the context of a patients clinical data using reasonable medical judgment. This website should not be used as a substitute for the advice of a licensed physician ...
This information is intended for physicians and related personnel, who understand that medical information is often imperfect, and must be interpreted in the context of a patients clinical data using reasonable medical judgment. This website should not be used as a substitute for the advice of a licensed physician ...
Wet-lab validated real-time PCR primer assays for your biological pathway of interest. Select your gene target of interest using an interactive pathway map, and select your plate.
The case and the entity will be discussed at the upcoming 2014 Dermpedia Comprehensive Review of Cutaneous Hematopathology in Scottsdale, AZ.. ...
HLDA WorkshopHLDA V-WS Code B070Quantity100 testsVolume2ImmunogenMOLT-4 (human T-ALL cell line)Background InformationCD81 (TAPA-1), a member of the...
This study tests the effectivity and tolerability of treatment with alemtuzumab (MabCampath) in patients with relapsed or refractory T-cell acute lymphoblastic leukemia (T-ALL) or T-lymphoblastic lymphoma. In Arm A, patients with refractory relapse receive a 2 week treatment with MabCampath followed by remission evaluation. In case of insufficient response, treatment with cladribine is added. In Arm B, patients with molecular relapse (minimal residual disease) receive a 4 week treatment with MabCampath followed by remission evaluation. In both arms, treatment is continued in case of response for up to two months ...
10048 Background: T-cell acute lymphoblastic leukemia (T-ALL) is representing 10-15% of pediatric ALL. The use of more intensive treatments and risk adapted therapy have significantly improved the outcome of patients with T-ALL and event-free survival rate of 60-70% are now reported in children. Our published data showed that T-ALL phenotype patients fared poorly with 5 year survival of 27% versus 83% for precursor B-ALL (Recent Advances Research Update: 2006, 7; 1, P 51-56). OBJECTIVES We reviewed all patients diagnosed with T-ALL to assess risk classification according to NCI criteria, type of therapy received, overall survival and causes of mortality. METHODS Retrospective review of all patients files diagnosed with T-ALL from 1989 until now with data collection including; sex, age, white cell count (WBCs), CNS disease, type of protocol used, length of survival, overall survival, cause of death (toxic, disease). RESULTS Over the last 20 years, T-ALL cases registered were 52/460 (11%) of all ALL
Transgenic non-human mammals that reproduce the human pathology that is of stem cell origin, for example, chromosomal anomalies associated with chronic myeloid leukaemia, B-cell acute lymphoblastic leukaemia, T-cell acute lymphoblastic leukaemia, or with the migration of haematopoietic or embryonic stem calls, using as a strategy the expression of the genes involved in said pathology in human beings by means of a promoter that directs the expression of a transgene in Sca-1|+| cells. Said transgenic animals constitute a model for the study of said diseases and for the evaluation of useful compounds for the treatment and/or prevention of said diseases.
For long, T-cell acute lymphoblastic leukemia (T-ALL) remained in the shadow of precursor B-ALL because it was more seldom, and showed a normal karyotype in more than 50% of cases. The last decennia, intense research has been carried out on different fronts. On one side, development of normal thymocyte and its regulation mechanisms have been studied in multiple mouse models and subsequently validated. On the other side, molecular cytogenetics (fluorescence in situ hybridization) and mutation analysis revealed cytogenetically cryptic aberrations in almost all cases of T-ALL. Also, expression microarray analysis disclosed gene expression signatures that recapitulate specific stages of thymocyte development. Investigations are still very much actual, fed by the discovery of new genetic aberrations. In this review, we present a summary of the current cytogenetic changes associated with T-ALL. The genes deregulated by translocations or mutations appear to encode proteins that are also implicated in ...
T-cell acute lymphoblastic leukemia (T-ALL) is a lymphoid disorder that results from an over proliferation of immature lymphocytes in the blood and bone marrow. It has been determined that 60% of patients stricken with T-ALL aberrantly express TAL-1 and have been shown to respond poorly to chemotherapy. This research sought to determine if TAL-1 influences the expression of the Bcl-2 family members Bcl-2 (anti-apoptotic), Bad and Bax (pro-apoptotic). TAL-1 and Bcl-2 levels were elevated while Bad and Bax levels were lower in etoposide-treated Jurkat cells as compared to TRAIL-treated and dual-treated Jurkat cells in which TAL-1 and Bcl-2 levels were lower while Bad and Bax levels were elevated. These results suggest TAL-1 up-regulates Bcl-2 and suppress Bad and Bax expression in response to etoposide treatment, thus inducing an anti-apoptotic response in the cell. These results also suggest that TRAIL and the dual treatment of etoposide and TRAIL down-regulates TAL-1 and Bcl-2 expression while ...
This randomized phase III trial compares how well combination chemotherapy works when given with or without bortezomib in treating patients with newly diagnosed T-cell acute lymphoblastic leukemia or stage II-IV T-cell lymphoblastic lymphoma. Bortezomib may help reduce the number of leukemia or lymphoma cells by blocking some of the enzymes needed for cell growth. It may also help chemotherapy work better by making cancer cells more sensitive to the drugs. It is not yet known if giving standard chemotherapy with or without bortezomib is more effective in treating T-cell acute lymphoblastic leukemia and T-cell lymphoblastic lymphoma ...
TY - JOUR. T1 - Germline IKAROS mutation associated with primary immunodeficiency that progressed to T-cell acute lymphoblastic leukemia. AU - Yoshida, N.. AU - Sakaguchi, H.. AU - Muramatsu, H.. AU - Okuno, Y.. AU - Song, C.. AU - Dovat, S.. AU - Shimada, A.. AU - Ozeki, M.. AU - Ohnishi, H.. AU - Teramoto, T.. AU - Fukao, T.. AU - Kondo, N.. AU - Takahashi, Y.. AU - Matsumoto, K.. AU - Kato, K.. AU - Kojima, S.. PY - 2017/5/1. Y1 - 2017/5/1. UR - http://www.scopus.com/inward/record.url?scp=85011620448&partnerID=8YFLogxK. UR - http://www.scopus.com/inward/citedby.url?scp=85011620448&partnerID=8YFLogxK. U2 - 10.1038/leu.2017.25. DO - 10.1038/leu.2017.25. M3 - Letter. C2 - 28096536. AN - SCOPUS:85011620448. VL - 31. SP - 1221. EP - 1223. JO - Leukemia. JF - Leukemia. SN - 0887-6924. IS - 5. ER - ...
... , Authors: Dessen P. Published in: Atlas Genet Cytogenet Oncol Haematol.
Leukemias and lymphomas of the T cell origin are often aggressive malignancies that are associated with a wide range of molecular defects in the T cell lineage (1, 2). In pediatric T cell acute lymphoblastic leukemia (T-ALL), for example, the most common molecular abnormalities are presented by mutations or silencing of the cdkn2a/2b genes that block expression of the p15INK4 and p16INK4 cell cycle suppressors (3-5) and prevent production of the p14ARF activator of p53 (1). Other prominent flaws in T-ALL molecular machinery also include Notch1 receptor-activating mutations (6, 7), inactivating mutations of Notch negative regulator, Fbxw7 (8-10), and of the inhibitor of PI3K signaling, the PTEN phosphatase (11). Alternatively, among lymphoid malignancies, cutaneous T cell lymphomas are characterized by frequent mutations in the nav3 gene (12), by the constitutive activation of STAT3 (13), by the overexpression of the CCR10 receptor (14), of JunB (15), and of the antiapoptotic protein Mcl-1 (16). ...
Current chemotherapies for T cell acute lymphoblastic leukemia (T-ALL) efficiently reduce tumor mass. Nonetheless, disease relapse attributed to survival of preleukemic stem cells (pre-LSCs) is associated with poor prognosis. Herein, we provide direct evidence that pre-LSCs are much less chemosensitive to existing chemotherapy drugs than leukemic blasts because of a distinctive lower proliferative state. Improving therapies for T-ALL requires the development of strategies to target pre-LSCs that are absolutely dependent on their microenvironment. Therefore, we designed a robust protocol for high-throughput screening of compounds that target primary pre-LSCs maintained in a niche-like environment, on stromal cells that were engineered for optimal NOTCH1 activation. The multiparametric readout takes into account the intrinsic complexity of primary cells in order to specifically monitor pre-LSCs, which were induced here by the ...
T cell acute lymphoblastic leukemia (T-ALL) is a disease induced by transformation of hematopoietic stem cells/progenitors. It afflicts mainly children and adol...
NOTCH1 is an attractive cancer target, particularly in T cell acute lymphoblastic leukemia (T-ALL), with activating mutations in this gene identified in more than 50% of cases. In this study, Roti et al. describe the synthesis, characterization, and validation of JQ-FT, a first-in-class NOTCH1 inhibitor that has dual selectivity for leukemia over normal cells and NOTCH1 mutants over wild-type receptors. ...
PDGFRB Fusion serves as an inclusion eligibility criterion in 15 clinical trials, of which 13 are open and 2 are closed. Of the trials that contain PDGFRB Fusion as an inclusion criterion, 3 are phase 1 (2 open), 1 is phase 1/phase 2 (1 open), 9 are phase 2 (8 open), 1 is phase 2/phase 3 (1 open), and 1 is phase 3 (1 open). Trials with PDGFRB Fusion in the inclusion eligibility criteria most commonly target acute lymphoblastic leukemia, B-cell acute lymphoblastic leukemia, adenocarcinoma of the gastroesophageal junction, B-cell lymphoblastic leukemia/lymphoma, and cancer [5]. ...
The goal of Part 1 of this clinical research study is to learn if PF-03084014 will have an effect on T-cell acute lymphoblastic leukemia or lymphoblastic leukemia. The goal of Part 2 of this study is to learn if PF-03084014 when given in combination with dexamethasone will have an effect on T-cell acute lymphoblastic leukemia or lymphoblastic leukemia. The safety and tolerability of this PF-03084014 will be tests in both parts.
Somatic ribosomal protein mutations have recently been described in cancer, yet their impact on cellular transcription and translation remains poorly understood. Here, we integrate mRNA sequencing, ribosome footprinting, polysomal RNA sequencing and mass spectrometry datasets from a mouse lymphoid cell model to characterize the T-cell acute lymphoblastic leukemia (T-ALL) associated ribosomal RPL10 R98S mutation. Surprisingly, RPL10 R98S induces changes in protein levels primarily through transcriptional rather than translation efficiency changes. Phosphoserine phosphatase (PSPH), encoding a key serine biosynthesis enzyme, was the only gene with elevated transcription and translation leading to protein overexpression. PSPH upregulation is a general phenomenon in T-ALL patient samples, associated with elevated serine and glycine levels in xenograft mice. Reduction of PSPH expression suppresses proliferation of T-ALL cell lines and their capacity to expand in mice. We identify ribosomal mutation ...
The TAL-1 gene is located on chromosome 1p32. In about 20% of T-cell acute lymphoblastic leukemias (T-ALL), this gene is disrupted in its 5 portion by a site-specific 100-kg deletion and is fused with the 5 part of the SIL gene, to form SIL-TAL-1 chimeric gene.. ...
Meeting Abstract: CT102 -- 105th Annual Meeting of the American-Association-for-Cancer-Research (AACR) -- APR 05-09, 2014 -- San Diego, CA -- S -- Source: ...
TY - JOUR. T1 - CXCL12-Producing Vascular Endothelial Niches Control Acute T Cell Leukemia Maintenance. AU - Pitt, Lauren A.. AU - Tikhonova, Anastasia N.. AU - Hu, Hai. AU - Trimarchi, Thomas. AU - King, Bryan. AU - Gong, Yixiao. AU - Sanchez-Martin, Marta. AU - Tsirigos, Aris. AU - Littman, Dan R.. AU - Ferrando, Adolfo A.. AU - Morrison, Sean J.. AU - Fooksman, David R.. AU - Aifantis, Iannis. AU - Schwab, Susan R.. PY - 2015/6/8. Y1 - 2015/6/8. N2 - The role of the microenvironment in Tcell acute lymphoblastic leukemia (T-ALL), or any acute leukemia, is poorly understood. Here we demonstrate that T-ALL cells are in direct, stable contact with CXCL12-producing bone marrow stroma. Cxcl12 deletion from vascular endothelial, but not perivascular, cells impeded tumor growth, suggesting a vascular niche for T-ALL. Moreover, genetic targeting of Cxcr4 in murine T-ALL after disease onset led to rapid, sustained disease remission, and CXCR4 antagonism suppressed human T-ALL in primary xenografts. ...
in Leukemia (2003), 17(9), 1851-1857. To accurately estimate the incidence of HOX11L2 expression, and determine the associated cytogenetic features, in T-cell acute lymphoblastic leukemia (T-ALL), the Groupe Francais de Cytogenetique ... [more ▼]. To accurately estimate the incidence of HOX11L2 expression, and determine the associated cytogenetic features, in T-cell acute lymphoblastic leukemia (T-ALL), the Groupe Francais de Cytogenetique Hematologique (GFCH) carried out a retrospective study of both childhood and adult patients. In total, 364 patients were included ( 211 children less than or equal to15 years and 153 adults), and 67 ( 18.5%) [ 47 children ( 22.4%) and 20 adults (13.1%)] were shown to either harbor the t(5; 14) q35; q32) translocation or express the HOX11L2 gene or both. Most of the common hematological parameters did not show significant differences within positive and negative populations, whereas the incidence of CD1a+/CD10+ and cytoplasmic CD3+ patients was significantly ...
To assess whether the mutations form aberrant sites of MYB binding, we performed ChIP-seq for MYB and analyzed peaks of MYB enrichment at the LMO2 locus. There was a complete absence of MYB binding at the intermediate promoter in cells that were wild-type at this locus, suggesting that the presence of the single native MYB motif in itself is insufficient to recruit MYB. In contrast, both PF-382 and DU.528 cells that harbor dual MYB motifs displayed precisely aligned MYB binding at the mutation site (Figure 1B). To determine whether the mutations affected promoter usage, we performed rapid amplification of 5′ complementary DNA ends in LMO2 mutant and wild-type cell lines by using a common primer in exon 6 capable of capturing the transcription start site of all LMO2 isoforms. Whereas the majority (73%) of 5′ capped transcripts in Loucy cells originated from the proximal promoter, both PF-382 and DU.528 cells demonstrated preferential usage of the recently described intermediate promoter (75% ...
During the early phases (phases 1 and 2), researchers assess safety, side effects, optimal dosages and risks/benefits. In the later phase (phase 3), researchers study whether the treatment works better than the current standard therapy. They also compare the safety of the new treatment with that of current treatments. Phase 3 trials include large numbers of people to make sure that the result is valid. There are also less common very early (phase 0) and later (phase 4) phases. Phase 0 trials are small trials that help researchers decide if a new agent should be tested in a phase 1 trial. Phase 4 trials look at long-term safety and effectiveness, after a new treatment has been approved and is on the market. ...
TY - JOUR. T1 - Clinical characteristics and outcomes of previously untreated patients with adult onset T-acute lymphoblastic leukemia and T-lymphoblastic lymphoma with hyper-CVAD based regimens. AU - Jain, Preetesh. AU - Kantarjian, Hagop. AU - Jain, Nitin. AU - Short, Nicholas J.. AU - Yin, Cameron C.. AU - Kanagal-Shamanna, Rashmi. AU - Khoury, Joseph. AU - Konopleva, Marina. AU - Sasaki, Koji. AU - Kadia, Tapan M.. AU - Garris, Rebecca. AU - Pierce, Sherry. AU - Estrov, Zeev. AU - Wierda, William. AU - Cortes, Jorge. AU - OBrien, Susan. AU - Ravandi, Farhad. AU - Jabbour, Elias. PY - 2017/10. Y1 - 2017/10. UR - http://www.scopus.com/inward/record.url?scp=85026454675&partnerID=8YFLogxK. UR - http://www.scopus.com/inward/citedby.url?scp=85026454675&partnerID=8YFLogxK. U2 - 10.1002/ajh.24833. DO - 10.1002/ajh.24833. M3 - Letter. C2 - 28646517. AN - SCOPUS:85026454675. VL - 92. SP - E595-E597. JO - American Journal of Hematology. JF - American Journal of Hematology. SN - 0361-8609. IS - ...
Another project, headed by Wenyi Wei was focused on researching a particular disease: T-cell acute lymphoblastic leukemia. With this disease, cells have a cocktail of proteins that should cause them to self-destruct but do not do so. Researchers looked into why this occurred and found that these cells lacked the FBW7 gene and without this, they did not break down MCL1 which was a necessary step in cell death. Wei connected this to drug resistance when T-ALL cells that were treated with drugs that targeted cell survivability-pathways were found to have lowered levels of MCL1 also. To try to fix this, Wei treated the cells with a drug that lowered MCL1 drugs and restored sensitivity to treatment.. ...
During the annual meeting of the American Association for Cancer Research (AACR), the CT078 test results showed that the majority of adult patients with recurrent B cell acute lymphoblastic leukemia…
The Slettos, who live in Brandon, were sent to Childrens Hospital in Minneapolis.. There, doctors diagnosed Kaidence with T-cell acute lymphoblastic leukemia, also known as T-ALL. T-ALL is an acute type of leukemia, which means it is aggressive and progresses quickly. It affects the system in the body which produces stem cells, especially a type of white blood cell called T lymphocytes.. Doctors also found a mass in her chest that was pushing on her left lung, causing it to partially collapse. Because of this, Kaidence was placed in a medically induced coma and put on a ventilator to help her breathe. Chemotherapy was started at this point.. On Wednesday, Dec. 27, she was taken out of the induced coma. Adrianna Sletto says the cancer is curable, but it will be a long road for her family. In addition to Kaidence, she and her husband, Kyle, have a 5-year-old and a baby on the way. ...
Despite great strides in treating childhood leukemia, a form of the disease called T-cell acute lymphoblastic leukemia (T-ALL) poses special challenges because of the high risk of leukemic cells invading the brain and spinal ...
Rahman S, Magnussen M, León TE, Farah N, Li Z, Abraham BJ, Alapi KZ, Mitchell RJ, Naughton T, Fielding AK, Pizzey A, Bustraan S, Allen C, Popa T, Pike-Overzet K, Garcia-Perez L, Gale RE, Linch DC, Staal FJT, Young RA, Look AT, Mansour MR. Activation of the LMO2 oncogene through a somatically acquired neomorphic promoter in T-cell acute lymphoblastic leukemia. Blood. 2017 06 15; 129(24):3221-3226 ...
TLX2兔多克隆抗体(ab51011)可与人样本反应并经WB, ELISA, IHC实验严格验证。中国75%以上现货,所有产品均提供质保服务,可通过电话、电邮或微信获得本地专属技术支持。
T cell acute lymphoblastic leukemia (T-ALL) is an aggressive cancer that is frequently associated with activating mutations in NOTCH1 and dysregulation of MYC. Here, we performed 2 complementary screens to identify FDA-approved drugs and drug-like small molecules with activity against T-ALL. We developed a zebrafish system to screen small molecules for toxic activity toward MYC-overexpressing thymocytes and used a human T-ALL cell line to screen for small molecules that synergize with Notch inhibitors. We identified the antipsychotic drug perphenazine in both screens due to its ability to induce apoptosis in fish, mouse, and human T-ALL cells. Using ligand-affinity chromatography coupled with mass spectrometry, we identified protein phosphatase 2A (PP2A) as a perphenazine target. T-ALL cell lines treated with perphenazine exhibited rapid dephosphorylation of multiple PP2A substrates and subsequent apoptosis. Moreover, shRNA knockdown of specific PP2A subunits attenuated perphenazine activity, ...
Asparaginase is a critical agent in the treatment of ALL. This enzyme deaminates asparagine, interfering with protein synthesis and resulting in cell death as lymphoblasts are deficient in asparagine synthetase. Eryaspase is a dispersion of homologous red blood cells (RBCs) encapsulating L-asparaginase formulated in a preservative solution for infusion. The formulation of eryaspase has evolved during its development. Two sources of L-asparaginase (drug substance) from Medac GmbH can be used as raw material and encapsulated in the RBCs: native (Kidrolase®) or recombinant L-asparaginase (Spectrila®). This study is designed to investigate the PK comparability of both eryaspase formulations: native or recombinant asparaginase as the starting material, when administered as monotherapy and in combination with chemotherapy during induction and consolidation phases for the treatment of children and young adults presenting with ALL/LBL. ...
Several caged Garcinia xanthone natural products have potent bioactivity and a documented value in traditional eastern medicine. Previous synthesis and SAR studies of these natural products resulted in the identification of the pharmacophore represented by the structure of cluvenone. In the current study, we examined the anti-cancer activity of cluvenone and conducted gene expression profiling and pathway analyses. Cluvenone was found to induce apoptosis in T-cell acute lymphoblastic leukemia cells (EC50 = 0.25 uM) and had potent growth inhibitory activity against the NCI60 cell panel, including those that are multi-drug resistant, with a GI50 range of 0.1 uM - 2.7 uM. Importantly, cluvenone was about 5-fold more potent against a primary B-cell acute lymphoblastic leukemia compared to peripheral blood mononuclear cells (PBMC) from normal donors suggesting that it has significant tumor selectivity. Comparison of cluvenones growth inhibitory profile to those in the NCI database revealed that ...
On-target drug delivery remains a challenge in cancer precision medicine; it is difficult to deliver a targeted therapy to cancer cells without incurring toxicity to normal tissues. The SERCA (sarco-endoplasmic reticulum Ca2+ ATPase) inhibitor thapsigargin inhibits mutant NOTCH1 receptors compared with wild type in T cell acute lymphoblastic leukemia (T-ALL), but its administration is predicted to be toxic in humans. Leveraging the addiction of ALL to folic acid, we conjugated folate to an alcohol derivative of thapsigargin via a cleavable ester linkage. JQ-FT is recognized by folate receptors on the plasma membrane and delivered into leukemia cells as a potent antileukemic agent. In mechanistic and translational models of T-ALL, we demonstrate NOTCH1 inhibition in vitro and in vivo. These proof-of-concept studies support the further optimization of this first-in-class NOTCH1 inhibitor with dual selectivity: leukemia over normal cells and NOTCH1 mutants over wild-type receptors. Furthermore, ...