Acquired dependence of acute myeloid leukemia on the DEAD-box RNA helicase DDX5 Journal Article
| Authors: | Mazurek, A.; Park, Y.; Miething, C.; Wilkinson, J.; Gillis, J.; Lowe, S.; Vakoc, C.; Stillman, B. |
| Article Title: | Acquired dependence of acute myeloid leukemia on the DEAD-box RNA helicase DDX5 |
| Abstract: | Acute myeloid leukemia (AML) therapy involves compounds that are cytotoxic to both normal andcancer 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 invitro and AML progression invivo 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 invivo, we show that DDX5 is dispensable for normal hematopoiesis and tissue homeostasis. These results validate DDX5 as a potential target for blocking AML. © 2014 The Authors. |
| Keywords: | controlled study; protein expression; unclassified drug; acute granulocytic leukemia; human cell; cancer growth; nonhuman; cell proliferation; mouse; cell death; protein bcl 2; apoptosis; bone marrow; protein depletion; protein targeting; animal experiment; animal model; in vivo study; cytotoxicity; in vitro study; dead box protein; leukemia cell; reactive oxygen metabolite; inhibition kinetics; hematopoiesis; down regulation; oxidative stress; homeostasis; 4 [4 (4' chloro 2 biphenylylmethyl) 1 piperazinyl] n [4 [3 dimethylamino 1 (phenylthiomethyl)propylamino] 3 nitrobenzenesulfonyl]benzamide; glucose metabolism; acetylcysteine; human; priority journal; article; dead box rna helicase ddx5; myeloid leukemia cell line |
| Journal Title: | Cell Reports |
| Volume: | 7 |
| Issue: | 6 |
| ISSN: | 2211-1247 |
| Publisher: | Cell Press |
| Date Published: | 2014-06-26 |
| Start Page: | 1887 |
| End Page: | 1899 |
| Language: | English |
| DOI: | 10.1016/j.celrep.2014.05.019 |
| PROVIDER: | scopus |
| PMCID: | PMC4100070 |
| PUBMED: | 24910429 |
| DOI/URL: | |
| Notes: | Export Date: 1 August 2014 -- Source: Scopus |
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