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Blood. 2010 Nov 18;116(20):4284-7. doi: 10.1182/blood-2010-04-279125. Epub 2010 Jul 12.

Treatment with the Bcl-xL inhibitor ABT-737 in combination with interferon α specifically targets JAK2V617F-positive polycythemia vera hematopoietic progenitor cells.

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1
Tisch Cancer Institute and Department of Medicine, Mount Sinai School of Medicine, New York, NY, USA.

Abstract

Polycythemia vera (PV) treatment with interferon α (IFNα) is frequently limited by dose-related toxicity. PV CD34(+) cells are characterized by overexpression of Bcl-xL, which can be antagonized by ABT-737 leading to apoptosis. We explored the effects of ABT-737 and IFNα on PV hematopoiesis. Both IFNα and ABT-737 alone or in combination had a modest effect on normal hematopoiesis but each individually were able to markedly induce PV CD34(+) cell apoptosis and suppress hematopoietic colony formation. The inhibitory activities of these agents in combination were greater against PV hematopoiesis than either agent alone. The exposure of PV CD34(+) cells to low doses of IFNα and ABT-737 in combination resulted in the reduction of the proportion of JAK2V617F(+) colonies similar to that observed with higher doses of IFNα. These data provide the rationale for combination therapy with low doses of IFNα and a BH3 mimetic for patients with PV.

PMID:
20625010
PMCID:
PMC2993627
DOI:
10.1182/blood-2010-04-279125
[Indexed for MEDLINE]
Free PMC Article
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