| First Author | Deshpande S | Year | 2013 |
| Journal | Stem Cells | Volume | 31 |
| Issue | 8 | Pages | 1683-95 |
| PubMed ID | 23681919 | Mgi Jnum | J:199718 |
| Mgi Id | MGI:5504541 | Doi | 10.1002/stem.1419 |
| Citation | Deshpande S, et al. (2013) KIT receptor gain-of-function in hematopoiesis enhances stem cell self-renewal and promotes progenitor cell expansion. Stem Cells 31(8):1683-95 |
| abstractText | The KIT receptor tyrosine kinase has important roles in hematopoiesis. We have recently produced a mouse model for imatinib resistant gastrointestinal stromal tumor (GIST) carrying the Kit(V558Delta) and Kit(T669I) (human KIT(T670I) ) mutations found in imatinib-resistant GIST. The Kit(V558Delta;T669I/+) mice developed microcytic erythrocytosis with an increase in erythroid progenitor numbers, a phenotype previously seen only in mouse models of polycythemia vera with alterations in Epo or Jak2. Significantly, the increased hematocrit observed in Kit(V558Delta;T669I/+) mice normalized upon splenectomy. In accordance with increased erythroid progenitors, myeloerythroid progenitor numbers were also elevated in the Kit(V558Delta;T669I/+) mice. Hematopoietic stem cell (HSC) numbers in the bone marrow (BM) of Kit(V558Delta;T669I/+) mice were unchanged in comparison to wild-type mice. However, increased HSC numbers were observed in fetal livers and the spleen and peripheral blood of adult Kit(V558Delta;T669I/+) mice. Importantly, HSC from Kit(V558Delta;T669I/+) BM had a competitive advantage over wild-type HSC. In response to 5-fluorouracil treatment, elevated numbers of dividing Lin(-) Sca(+) cells were found in the Kit(V558Delta;T669I/+) BM compared to wild type. Our study demonstrates that signaling from the Kit(V558Delta;T669I/+) receptor has important consequences in hematopoiesis enhancing HSC self-renewal and resulting in increased erythropoiesis. |
