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 Blood, 12 February 2009, Vol. 113, No. 7, pp. 1455-1463.
Prepublished online as a Blood First Edition Paper on September 25, 2008; DOI 10.1182/blood-2008-05-159905.

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HEMATOPOIESIS AND STEM CELLS

Mll5 contributes to hematopoietic stem cell fitness and homeostasis

Yan Zhang1, Jasmine Wong2, Mark Klinger1, Mary T. Tran2, Kevin M. Shannon2, and Nigel Killeen1

Departments of 1 Microbiology and Immunology and 2 Pediatrics, University of California, San Francisco

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.


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Related Article in Blood Online:

MLL5 governs hematopoiesis: a step closer
Han Liu, Todd D. Westergard, and James J.-D. Hsieh
Blood 2009 113: 1395-1396. [Full Text] [PDF]



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[Abstract] [Full Text] [PDF]

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 BloodHome page
H. Liu, T. D. Westergard, and J. J.-D. Hsieh
MLL5 governs hematopoiesis: a step closer
Blood, February 12, 2009; 113(7): 1395 - 1396.
[Full Text] [PDF]


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