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Here, we used a knock\u2010in JAK2V617F mouse model and confirmed that Bcl\u2010xL was overexpressed in erythroid progenitors. The myeloproliferative neoplasm (MPN)\u2010induced phenotype in the peripheral blood by conditional knock\u2010in of JAK2V617F was abrogated by conditional knockout of <jats:italic>Bcl2l1<\/jats:italic>, which presented anemia and thrombocytopenia independently of JAK2 mutation status. <jats:italic>Mx1\u2010Cre Jak2V617<jats:sup>W\/VF<\/jats:sup>\/Bcl2l1<jats:sup>f\/f<\/jats:sup><\/jats:italic> mice presented persistent splenomegaly as a result of extramedullary hematopoiesis and pro\u2010apoptotic stimuli in terminally differentiated erythroid progenitors. The pan\u2010BH3 mimetic inhibitor obatoclax showed superior cytotoxicity in JAK2V617F cell models, and reduced clonogenic capacity in ex vivo assay using Vav\u2010Cre Jak2V617F bone marrow cells. Both ruxolitinib and obatoclax significantly reduced spleen weights in a murine Jak2V617F MPN model but did not show additive effect. The tumor burden reduction was observed with either ruxolitinib or obatoclax in terminal differentiation stage neoplastic cells but not in myeloid\u2010erythroid precursors. Therefore, disrupting the BCL2 balance is not sufficient to treat MPN at the stem cell level, but it is certainly an additional option for controlling the critical myeloid expansion of the disease.<\/jats:p>","DOI":"10.1111\/cas.15210","type":"journal-article","created":{"date-parts":[[2021,11,22]],"date-time":"2021-11-22T17:33:08Z","timestamp":1637602388000},"page":"597-608","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Suppression of multiple anti\u2010apoptotic BCL2 family proteins recapitulates the effects of JAK2 inhibitors in JAK2V617F driven myeloproliferative neoplasms"],"prefix":"10.1111","volume":"113","author":[{"given":"Hisashi","family":"Takei","sequence":"first","affiliation":[{"name":"Department of Medicine Beth Israel Deaconess Medical Center and Harvard Medical School  Boston Massachusetts USA"},{"name":"Department of Hematology Gunma University Graduate School of Medicine  Maebashi\u2010shi 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Bianco","sequence":"additional","affiliation":[{"name":"Department of Medical Images, Hematology, and Clinical Oncology Ribeir\u00e3o Preto Medical School University of S\u00e3o Paulo, Ribeir\u00e3o Preto  S\u00e3o Paulo Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert S.","family":"Welner","sequence":"additional","affiliation":[{"name":"Department of Medicine Division Hematology\/Oncology University of Alabama at Birmingham  Birmingham Alabama USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuta","family":"Mishima","sequence":"additional","affiliation":[{"name":"Department of Clinical Medicine Faculty of Medicine Transborder Medical Research Center University of Tsukuba  Tsukuba Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ikei S.","family":"Kobayashi","sequence":"additional","affiliation":[{"name":"Department of Medicine Beth Israel Deaconess Medical Center and Harvard Medical School  Boston Massachusetts 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