Literature DB >> 23036488

Mechanisms of apoptosis induction by simultaneous inhibition of PI3K and FLT3-ITD in AML cells in the hypoxic bone marrow microenvironment.

Linhua Jin1, Yoko Tabe, Hongbo Lu, Gautam Borthakur, Takashi Miida, Hagop Kantarjian, Michael Andreeff, Marina Konopleva.   

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.
Copyright © 2012 Elsevier Ltd. All rights reserved.

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Year:  2012        PMID： 23036488      PMCID： PMC3572533          DOI： 10.1016/j.canlet.2012.09.020

Source DB:  PubMed          Journal:  Cancer Lett        ISSN： 0304-3835            Impact factor:   8.679


  50 in total

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