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Blood. 2009 Feb 12;113(7):1455-63. doi: 10.1182/blood-2008-05-159905. Epub 2008 Sep 25.

MLL5 contributes to hematopoietic stem cell fitness and homeostasis.

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  • 1Department of Microbiology and Immunology, University of California, San Francisco, CA 94143-0414, USA.

Abstract

MLL5 is a novel trithorax group gene and a candidate tumor suppressor gene located within a 2.5-Mb interval of chromosome band 7q22 that frequently is deleted in human myeloid malignancy. Here we show that inactivation of the Mll5 gene in mice results in a 30% reduction in the average representation of hematopoietic stem cells and in functional impairment of long-term hematopoietic repopulation potential under competitive conditions. Bone marrow cells from Mll5-deficient mice were defective in spleen colony-forming assays, and the mutant mice showed enhanced susceptibility to 5-fluorouracil-induced myelosuppression. Heterozygous and homozygous Mll5 mutant mice did not spontaneously develop hematologic cancers, and loss of Mll5 did not alter the phenotype of a fatal myeloproliferative disorder induced by oncogenic Kras in vivo. Collectively, the data reveal an important role for Mll5 in HSC homeostasis and provide a basis for further studies to explore its role in leukemogenesis.

Comment in

PMID:
18818388
[PubMed - indexed for MEDLINE]
PMCID:
PMC2644073
Free PMC Article

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