Acquired Dependence of Acute Myeloid Leukemia on the DEAD-Box RNA Helicase DDX5

Mazurek, A., Park, Y., Miething, C., Wilkinson, J. E., Gillis, J., Lowe, S. W, Vakoc, C. R, Stillman, B. (2014) Acquired Dependence of Acute Myeloid Leukemia on the DEAD-Box RNA Helicase DDX5. Cell Reports, 7 (6). pp. 1887-1899. ISSN 2211-1247

URL: http://www.ncbi.nlm.nih.gov/pubmed/24910429
DOI: 10.1016/j.celrep.2014.05.019

Abstract

Summary 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.

Item Type: Paper
Subjects: bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types > enzymes > helicase
diseases & disorders > cancer > cancer types > leukemia
CSHL Authors:
Communities: CSHL Cancer Center Program > Gene Regulation and Cell Proliferation
CSHL labs > Gillis Lab
CSHL labs > Stillman lab
CSHL labs > Vakoc lab
CSHL Cancer Center Shared Resources > Bioinformatics Service
Highlight: Stillman, Bruce W.
Depositing User: Matt Covey
Date Deposited: 13 Jun 2014 14:58
Last Modified: 20 Jun 2017 16:00
PMCID: PMC4100070
Related URLs:
URI: http://repository.cshl.edu/id/eprint/30304

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