| First Author | Haneline LS | Year | 2006 |
| Journal | Blood | Volume | 107 |
| Issue | 4 | Pages | 1375-82 |
| PubMed ID | 16239435 | Mgi Jnum | J:125793 |
| Mgi Id | MGI:3759932 | Doi | 10.1182/blood-2005-05-1985 |
| Citation | Haneline LS, et al. (2006) Genetic reduction of class IA PI-3 kinase activity alters fetal hematopoiesis and competitive repopulating ability of hematopoietic stem cells in vivo. Blood 107(4):1375-82 |
| abstractText | Class I(A) phosphatidylinositol-3 kinase (PI-3K) is a lipid kinase, which is activated in blood cells by hematopoietic growth factors. In vitro experiments using chemical inhibitors of PI-3K suggest that this kinase is potentially important for hematopoietic stem and progenitor cell (HSC/P) function, and recent studies identify PI-3K as a therapeutic target in treating different leukemias and lymphomas. However, the role of PI-3K in regulating fetal liver or adult hematopoiesis in vivo is unknown. Therefore, we examined PI-3K-deficient embryos generated by a targeted deletion of the p85alpha and p85beta regulatory subunits of PI-3K (p85alpha-/-p85beta+/-). The absolute frequency and number of hematopoietic progenitor cells were reduced in p85alpha-/- p85beta+/- fetal livers compared with wild-type (WT) controls. Further, p85alpha-/-p85beta+/- fetal liver hematopoietic stem cells (HSCs) had decreased multilineage repopulating ability in vivo compared with WT controls in competitive repopulation assays. Finally, purified p85alpha-/-p85beta+/- c-kit+ cells had a decrease in proliferation in response to kit ligand (kitL), a growth factor important for controlling HSC function in vivo. Collectively, these data identify PI-3K as an important regulator of HSC function and potential therapeutic target in treating leukemic stem cells. |
