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

ABSTRACT: 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 erythroid progenitors. The myeloproliferative neoplasm (MPN)-induced phenotype in the peripheral blood by conditional knock-in of JAK2V617F was abrogated by conditional knockout of Bcl2l1, which presented anemia and thrombocytopenia independently of JAK2 mutation status. Mx1-Cre Jak2V617^W/VF /Bcl2l1^f/f mice presented persistent splenomegaly as a result of extramedullary hematopoiesis and pro-apoptotic stimuli in terminally differentiated erythroid progenitors. The pan-BH3 mimetic i

SUBMITTER: Takei H 

PROVIDER: S-EPMC8819353 | biostudies-literature | 2022 Feb

REPOSITORIES: biostudies-literature