NDLI: HOXA9 is required for survival in human MLL-rearranged acute leukemias

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HOXA9 is required for survival in human MLL-rearranged acute leukemias

Content Provider	Scilit
Author	Faber, Joerg Krivtsov, Andrei V. Stubbs, Matthew C. Wright, Renee Davis, Tina N. Heuvel-Eibrink, Marry Van Den Zwaan, Christian M. Kung, Andrew L. Armstrong, Scott A.
Copyright Year	2009
Description	Leukemias that harbor translocations involving the mixed lineage leukemia gene (MLL) possess unique biologic characteristics and often have an unfavorable prognosis. Gene expression analyses demonstrate a distinct profile for MLL-rearranged leukemias with consistent high-level expression of select Homeobox genes, including HOXA9. Here, we investigated the effects of HOXA9 suppression in MLL-rearranged and MLL-germline leukemias using RNA interference. Gene expression profiling after HOXA9 suppression demonstrated co–down-regulation of a program highly expressed in human MLL-AML and murine MLL-leukemia stem cells, including HOXA10, MEIS1, PBX3, and MEF2C. We demonstrate that HOXA9 depletion in 17 human AML/ALL cell lines (7 MLL-rearranged, 10 MLL-germline) induces proliferation arrest and apoptosis specifically in MLL-rearranged cells (P = .007). Similarly, assessment of primary AMLs demonstrated that HOXA9 suppression induces apoptosis to a greater extent in MLL-rearranged samples (P = .01). Moreover, mice transplanted with HOXA9-depleted t(4;11) SEMK2 cells revealed a significantly lower leukemia burden, thus identifying a role for HOXA9 in leukemia survival in vivo. Our data indicate an important role for HOXA9 in human MLL-rearranged leukemias and suggest that targeting HOXA9 or downstream programs may be a novel therapeutic option.
Related Links	http://www.bloodjournal.org/content/113/11/2375.full.pdf
Ending Page	2385
Page Count	11
Starting Page	2375
DOI	10.1182/blood-2007-09-113597
Journal	Blood
Issue Number	11
Volume Number	113
Language	English
Publisher	American Society of Hematology
Publisher Date	2009-03-12
Access Restriction	Open
Subject Keyword	Research and Experimental Medicine Gene Expression Survival Mll Rearranged Leukemias Germline Apoptosis Journal: Blood (Vol- 117, Issue- 11)
Content Type	Text
Resource Type	Article

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