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Mll5 is Required for Hematopoietic Stem Cell Fitness and Homeostasis

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 is frequently deleted in human myeloid malignancy. Here we show that Mll5 is required for normal hematopoietic stem cell (HSC) homeostasis. Inactivation of the Mll5 gene in mice results in reduced cellularity of the long-term HSC compartment, which correlates with functional impairment of long-term 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 myeloprolferative 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. Keywords: Cell type comparision.

ORGANISM(S): Mus musculus

PROVIDER: GSE10817 | GEO | 2008/05/22

SECONDARY ACCESSION(S): PRJNA107415

REPOSITORIES: GEO

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