Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
2113177 | Cancer Letters | 2013 | 14 Pages |
Abstract
We investigated the antileukemia effects and molecular mechanisms of apoptosis induction by simultaneous blockade of PI3K and mutant FLT3 in AML cells grown under hypoxia in co-cultures with bone marrow stromal cells. Combined treatment with selective class I PI3K inhibitor GDC-0941 and sorafenib reversed the protective effects of bone marrow stromal cells on FLT3-mutant AML cells in hypoxia, which was associated with downregulation of Pim-1 and Mcl-1 expression levels. These findings suggest that combined inhibition of PI3K and FLT3-ITD may constitute a targeted approach to eradicating chemoresistant AML cells sequestered in hypoxic bone marrow niches.
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Authors
Linhua Jin, Yoko Tabe, Hongbo Lu, Gautam Borthakur, Takashi Miida, Hagop Kantarjian, Michael Andreeff, Marina Konopleva,