| First Author | Rosu-Myles M | Year | 2007 |
| Journal | Exp Hematol | Volume | 35 |
| Issue | 3 | Pages | 394-406 |
| PubMed ID | 17309820 | Mgi Jnum | J:123185 |
| Mgi Id | MGI:3717324 | Doi | 10.1016/j.exphem.2006.11.005 |
| Citation | Rosu-Myles M, et al. (2007) Loss of the tumor suppressor p15Ink4b enhances myeloid progenitor formation from common myeloid progenitors. Exp Hematol 35(3):394-406 |
| abstractText | OBJECTIVE: The tumor suppressor p15Ink4b (Ink4b) is a cell-cycle inhibitor that is inactivated in a high percentage of acute myeloid leukemia and myeloid dysplasia syndrome cases. Despite this, the role of Ink4b in hematopoiesis remains unclear. Here we examined the role of Ink4b in blood cell formation using Ink4b-deficient (Ink4b(-/-)) mice. METHODS: We compared the bone marrow (BM) of Ink4b(-/-) and wild-type mice using flow cytometric, colony-forming unit and competitive repopulating assays (CRA). The proliferation, differentiation, self-renewal, and apoptosis of progenitor cells were further compared by in vitro and in vivo methods. RESULTS: BM from Ink4b(-/-) mice contained increased numbers of granulocyte-monocyte progenitors and Gr-1(+) cells and showed a competitive advantage over wild-type cells in myeloid cell formation by CRA. Ink4b(-/-) progenitors did not demonstrate increased proliferation, self-renewing potential, or reduced apoptosis. Instead, Ink4b(-/-) common myeloid progenitors (CMPs) showed increased myeloid progenitor formation concomitant with reduced erythroid potential. CONCLUSIONS: This work establishes a role for Ink4b in regulating the differentiation of CMPs and indicates that loss of Ink4b enhances the formation of myeloid progenitors. |
