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MLL5 contributes to hematopoietic stem cell fitness and homeostasis.

Blood | Feb 12, 2009

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.

Pubmed ID: 18818388 RIS Download

Mesh terms: Animals | Antimetabolites, Antineoplastic | Apoptosis | Bone Marrow Transplantation | Cell Cycle | Cell Differentiation | Fluorouracil | Gene Expression | Hematopoiesis | Hematopoietic Stem Cells | Histone-Lysine N-Methyltransferase | Homeostasis | Integrases | Leukemia | Mice | Mice, Inbred C57BL | Mice, Knockout | Multipotent Stem Cells | Myeloid-Lymphoid Leukemia Protein | Proto-Oncogene Proteins p21(ras) | Spleen

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Associated grants

  • Agency: NCI NIH HHS, Id: P01 CA040046
  • Agency: NCI NIH HHS, Id: CA40046
  • Agency: NCI NIH HHS, Id: CA84221

Comparative Toxicogenomics Database (Data, Disease Annotation)

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