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Cell Rep. 2014 Jun 26;7(6):1887-99. doi: 10.1016/j.celrep.2014.05.019. Epub 2014 Jun 5.

Acquired dependence of acute myeloid leukemia on the DEAD-box RNA helicase DDX5.

Author information

1
Cold Spring Harbor Laboratory, 1 Bungtown Road, Cold Spring Harbor, NY 11724, USA.
2
Memorial Sloan-Kettering Cancer Center, 415 E. 68(th) Street, Box 373, New York, NY 10065, USA.
3
Unit for Laboratory Animal Medicine, University of Michigan, Ann Arbor, MI 48109, USA.
4
Cold Spring Harbor Laboratory, 1 Bungtown Road, Cold Spring Harbor, NY 11724, USA. Electronic address: stillman@cshl.edu.

Abstract

Acute myeloid leukemia (AML) therapy involves compounds that are cytotoxic to both normal and cancer cells, and relapsed AML is resistant to subsequent chemotherapy. Thus, agents are needed that selectively kill AML cells with minimal toxicity. Here, we report that AML is dependent on DDX5 and that inhibiting DDX5 expression slows AML cell proliferation in vitro and AML progression in vivo but is not toxic to cells from normal bone marrow. Inhibition of DDX5 expression in AML cells induces apoptosis via induction of reactive oxygen species (ROS). This apoptotic response can be blocked either by BCL2 overexpression or treatment with the ROS scavenger N-acetyl-L-cysteine. Combining DDX5 knockdown with a BCL2 family inhibitor cooperates to induce cell death in AML cells. By inhibiting DDX5 expression in vivo, we show that DDX5 is dispensable for normal hematopoiesis and tissue homeostasis. These results validate DDX5 as a potential target for blocking AML.

PMID:
24910429
PMCID:
PMC4100070
DOI:
10.1016/j.celrep.2014.05.019
[Indexed for MEDLINE]
Free PMC Article

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