Journal
EMBO JOURNAL
Volume 28, Issue 10, Pages 1492-1504Publisher
WILEY
DOI: 10.1038/emboj.2009.97
Keywords
c-Myb; differentiation commitment; haematopoietic stem cell; myeloproliferative disorder; self-renewal
Categories
Funding
- Wellcome Trust
- Leukaemia Research
- MRC [G0501688] Funding Source: UKRI
- Medical Research Council [G0501688, G9818340B] Funding Source: researchfish
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Murine haematopoietic stem cells (HSCs) are contained in the Kit(+)Sca1(+)Lin(-) (KSL) population of bone marrow and are able to repopulate lethally irradiated mice. Myeloproliferative disorders (MPDs) are thought to be clonogenic diseases arising at the level of the HSC. Here, we show that mice expressing low levels of the transcription factor c-Myb, as the result of genetic knockdown, develop a transplantable myeloproliferative phenotype that closely resembles the human disease essential thrombocythaemia (ET). Unlike wild-type cells, the KSL population in c-myb knockdown bone marrow cannot repopulate irradiated mice and does not transfer the disease. Instead, cells positive for Kit and expressing low to medium levels of CD11b acquire self-renewing stem cell properties and are responsible for the perpetuation of the myeloproliferative phenotype. The EMBO Journal (2009) 28, 1492-1504. doi:10.1038/emboj.2009.97; Published online 9 April 2009
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