KIT receptor gain-of-function in hematopoiesis enhances stem cell self-renewal and promotes progenitor cell expansion.

ABSTRACT: 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(V558Δ) and Kit(T669I) (human KIT(T670I) ) mutations found in imatinib-resistant GIST. The Kit(V558Δ;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(V558Δ;T669I/+) mice normalized upon splenectomy. In accordance with increased erythroid progenitors, myeloerythroid progenitor numbers were also elevated in the Kit(V558Δ;T669I/+) mice. Hematopoietic stem cell (HSC) numbers in the bone marrow (BM) of K

SUBMITTER: Deshpande S 

PROVIDER: S-EPMC3775897 | biostudies-literature | 2013 Aug

REPOSITORIES: biostudies-literature