Suppression of multiple anti-apoptotic BCL2 family proteins recapitulates the effects of JAK2 inhibitors in JAK2V617F driven myeloproliferative neoplasms

Several lines of research suggest that Bcl-xL-mediated anti-apoptotic effects may contribute to the pathogenesis of myeloproliferative neoplasms driven by JAK2V617F and serve as therapeutic target. Here, we used a knock-in JAK2V617F mouse model and confirmed that Bcl-xL was overexpressed in erythroi...

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Bibliographic Details
Main Authors:	Coelho-Silva, J.L (Author), Kobayashi, I.S (Author), Kobayashi, S.S (Author), Lima, K. (Author), Lobo de Figueiredo-Pontes, L. (Author), Machado-Neto, J.A (Author), Mantello Bianco, T. (Author), Mishima, Y. (Author), Mullally, A. (Author), Queiroz Arantes Rocha, A. (Author), Takei, H. (Author), Tavares Leal, C. (Author), Welner, R.S (Author)
Format:	Article
Language:	English
Published:	John Wiley and Sons Inc 2022
Subjects:	anemia animal animal cell animal experiment animal model animal tissue Animals antineoplastic activity apoptosis Article BCL2 family proteins Bcl2l1 protein, mouse bcl-X Protein BIM protein bone marrow cell bone marrow derived mononuclear cell bone morphogenetic protein CD3 antigen CD71 antigen Cell Line, Tumor cell proliferation Cell Proliferation cell survival Cell Survival controlled study disease model Disease Models, Animal drug cytotoxicity drug effect drug resistance Drug Resistance, Neoplasm endoglin enzyme inhibitor Enzyme Inhibitors erythroid precursor cell Erythroid Precursor Cells erythropoiesis ex vivo study extramedullary hematopoiesis flow cytometry gene expression level gene expression profiling gene mutation genetics histopathology human Humans indole derivative Indoles Jak2 protein, mouse JAK2V617F Janus kinase 2 Janus Kinase 2 Janus kinase 2 inhibitor male megakaryopoiesis messenger RNA metabolism Mice mouse mouse model mouse models mutation Mutation myeloproliferative disorder Myeloproliferative Disorders myeloproliferative neoplasm myeloproliferative neoplasms nitrile Nitriles nonhuman obatoclax pathology phenotype polyacrylamide gel electrophoresis protein BAD protein bcl 2 protein bcl x protein bcl xl protein function Proto-Oncogene Proteins c-bcl-2 pyrazole derivative Pyrazoles pyrimidine derivative Pyrimidines pyrrole derivative Pyrroles real time polymerase chain reaction receptor type tyrosine protein phosphatase C RNA sequencing ruxolitinib spleen weight splenomegaly STAT5 protein thrombocytopenia Tumor Burden tumor cell line tumor volume Western blotting
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Suppression of multiple anti-apoptotic BCL2 family proteins recapitulates the effects of JAK2 inhibitors in JAK2V617F driven myeloproliferative neoplasms

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