Swerdlow

Similarly, in primary B-ALL patient samples, a minority was sensitive to selective targeting of BCL-2, MCL-1, or BCL-XL alone; however, simultaneous targeting of MCL-1 and either BCL-2 (with venetoclax or S55746) or BCL-XL demonstrated potent killing in 15 of 24 and 9 of 20 of samples, respectively. Histopathology 2001; 38-62-67. To minimize the risk of ATLS in subsequent experiments, treatment was commenced at a lower tumor burden (median 1% engraftment) using lead-in and lower final doses of venetoclax. The purpose of this study was to evaluate the prognostic value of the "Hans classifier", and BCL2 and MYC protein expression and gene alterations in DLBCL patients treated with CHOP or R-CHOP chemotherapy over a 5-year period. (A) Irradiated NSG mice were transplanted with 1 × 106 primary B-ALL cells (Ph− 01-160-2015 or Ph+ 01-228-2012). Kim



Thanks to an extended follow-up, we also investigated prognostic factors that would predict relapse or extracutaneous spreading in PCFCL. J Cellular Pathol 1996;1:52-56. Results: Representative cases from each cohort are shown. Diffuse large B-cell lymphoma with MYC gene rearrangements: Current perspective on treatment of diffuse large B-cell lymphoma with MYC gene rearrangements; case series and review of the literature. The combination demonstrated greater efficacy than standard chemotherapeutics and TKIs in primary samples from adult B-ALL with Ph+ ALL, Ph-like ALL, and other B-ALL.

K, Example of case exhibiting large centroblast predominance (×400). Clipboard, Search History, and several other advanced features are temporarily unavailable. The gene for bcl-2 is located on chromosome 18. NLM Venetoclax up to 100 mg/kg with S63845 up to 12.5 mg/kg was well tolerated with no impact on blood counts or weight (supplemental Figure 3). L MH Staiger AM, Ziepert M, Horn H, Scott DW, Barth TFE, Bernd HW, Feller AC, Klapper W, Szczepanowski M, Hummel M, Stein H, Lenze D, Hansmann ML, Hartmann S, Möller P, Cogliatti S, Lenz G, Trümper L, Löffler M, Schmitz N, Pfreundschuh M, Rosenwald A, Ott G; German High-Grade Lymphoma Study Group. Goodlad A small/medium centrocytic cell population was associated with a higher probability of skin relapse in univariate (P = .008) and multivariate (P = .028) analysis, and BCL2 rearrangement detection was associated with secondary extracutaneous spreading (P = .05).

Among the six cases of SSIFCL, one exhibited a large-cell morphology, and five had a predominance of small/medium centrocytes. and D.T.H. This work has received funding support from Servier. Clinical and histologic (H&E-safranin) features of primary cutaneous follicle center lymphoma (PCFCL). Clinical and histologic data were collected together with staging and follow-up data. The grade of CIN correlates with the proportion of cells that are bcl-2 positive. MW

H&E, hematoxylin and eosin. C, Survival function (shared γ-frailty model), considering all cutaneous relapses, according to the presence of BCL2 rearrangement. Cervical intra-epithelial neoplasia. In addition, BCL-2 may assist in the separation of Burkitt’s lymphoma (which is BCL-2 negative) from Burkitt-like lymphoma (which is reported to be positive with BCL- 2 in 67% of cases). Child In contrast, TKI potentiation was not seen with either BH3-mimetic in CRLF2-rearranged Ph-like ALL cell lines, despite increased BIM expression following TKI exposure in both Ph+ and Ph-like ALL cell lines (supplemental Figure 1A). Van Dongen

In three cases, frozen skin touch imprints were hybridized as described before.17 FISH patterns were determined by analyzing 200 nonoverlapped nuclei as reported.7 Cases with a BCL2 breakpoint were then referred to as t(14;18)-positive FCL, because translocation partners other than IgH are exceedingly rarely affected in FCL.2. Mutated genes showed high BCL2 association in both subgroups. Proc Natl Acad Sci U S A 1986; 83:5214-8, Cleary ML, Smith SD,Sklar J. Cloning and structural analysis of cDNAs for bcl-2 and a hybrid bcl-2/immunoglobulin transcript resulting from the t(14;18) translocation. et al. The study was performed after patient information and consent, according to the guidelines of the French bioethical law and the Declaration of Helsinki principles.

Br J Haematol 1990; 76:58-64, Weiss LM, Warnke RA, Sklar J, et al. Epub 2017 May 19.
The 5-year OS was 61% in the R-CHOP compared to 38% in the CHOP group (p=0.007).

doi: https://doi.org/10.1182/bloodadvances.2019001416. The median follow-up was 39 months (range, 1–191 months). (2003). Patient material was obtained through the Tumor Bank of CHU Bordeaux and Cancéropôle Grand Sud Ouest. Br J Haematol 1990; 76:58-64, 22 Weiss LM, Warnke RA, Sklar J, et al. et al. HHS Kluin-Nelemans All 6 mice receiving the highest doses (venetoclax 100 mg/kg and S63845 25 mg/kg) remained well. Search for other works by this author on: New insights into the pathophysiology and therapy of adult acute lymphoblastic leukemia, ABT-199, a potent and selective BCL-2 inhibitor, achieves antitumor activity while sparing platelets, Targeting BCL2 with venetoclax in relapsed chronic lymphocytic leukemia, S55746 is a novel orally active BCL-2 selective and potent inhibitor that impairs hematological tumor growth, Structure-guided design of a selective BCL-X(L) inhibitor, The MCL1 inhibitor S63845 is tolerable and effective in diverse cancer models, Venetoclax combined with decitabine or azacitidine in treatment-naive, elderly patients with acute myeloid leukemia, Safety and efficacy of venetoclax in combination with navitoclax in adult and pediatric relapsed/refractory acute lymphoblastic leukemia and lymphoblastic lymphoma [abstract], Dysregulation of BCL-2 family proteins by leukemia fusion genes, MLL-rearranged acute lymphoblastic leukemias activate BCL-2 through H3K79 methylation and are sensitive to the BCL-2-specific antagonist ABT-199, Venetoclax responses of pediatric ALL xenografts reveal sensitivity of MLL-rearranged leukemia, Requirement for antiapoptotic MCL-1 in the survival of BCR-ABL B-lineage acute lymphoblastic leukemia, Targeting BCL-2 and ABL/LYN in Philadelphia chromosome-positive acute lymphoblastic leukemia, Oncogenic role and therapeutic targeting of ABL-class and JAK-STAT activating kinase alterations in Ph-like ALL, Ph-like acute lymphoblastic leukemia: a high-risk subtype in adults, Combining BH3-mimetics to target both BCL-2 and MCL1 has potent activity in pre-clinical models of acute myeloid leukemia, Deletion of IKZF1 and prognosis in acute lymphoblastic leukemia, Expression profiling of a hemopoietic cell survival transcriptome implicates osteopontin as a functional prognostic factor in AML, Diagnostic exercise: sudden death in a mouse with experimentally induced acute myeloid leukemia, Case series: acute tumor lysis syndrome in mutator mice with disseminated lymphoblastic lymphoma, © 2020 by The American Society of Hematology, Copyright ©2020 by American Society of Hematology, https://doi.org/10.1182/bloodadvances.2019001416.
Peripheral blood blast levels were compared with gauge efficacy and >25% hCD45+CD19+ defined as an event after animal ethics committee review. AW Belaud-Rotureau

The gene product is a25 kDa inner mitochondrial membrane protein which inhibits apoptosis, so extending cell survivial. Jansen Copyright © 2020 American Society for Clinical Pathology. Nevertheless, most of these cases express BCL2. Bcl-2 positive patients had more short overall survival times.

et al. Vergier YH 2016 May 13;473(4):821-827

Soubeyran Y

Tsujimoto Y,Croce CM Analysis of the structure, transcripts, and protein products of bcl-2, the gene involved in human follicular lymphoma.

PJ Notably, >50% of Ph+ and Ph− primary ALL samples were sensitive to combined BCL-2 and MCL-1 inhibition (Figure 1B; supplemental Table 1). NIH

-, Leukemia.  |  NLM Positivity for bcl-2 in a lymphoma is NOT evidence of follicular derivation. Pandya

, eds.


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