| First Author | Ingram DA | Year | 2003 |
| Journal | Blood | Volume | 101 |
| Issue | 5 | Pages | 1984-6 |
| PubMed ID | 12393498 | Mgi Jnum | J:82128 |
| Mgi Id | MGI:2451203 | Doi | 10.1182/blood-2002-08-2635 |
| Citation | Ingram DA, et al. (2003) Leukemic potential of doubly mutant Nf1 and Wv hematopoietic cells. Blood 101(5):1984-6 |
| abstractText | The development of molecularly targeted treatments of adult leukemias warrants investigation of these targets in similar pediatric leukemias. The NF1 tumor suppressor gene, which encodes a GTPase activating protein for p21(ras), is frequently inactivated in juvenile myelomonocytic leukemia (JMML). Other patients with JMML acquire activating RAS gene mutations. Recipient mice reconstituted with Nf1-/- fetal hematopoietic cells develop a myeloproliferative disease (MPD) that models the human disease. JMML arises from clonal expansion of a hematopoietic stem cell, and JMML cells and murine Nf1-/- hematopoietic cells are hypersensitive to granulocyte macrophage-colony stimulating factor and KitL, the ligand for c-kit. We generated embryos doubly mutant for the Wv allele of c-kit and Nf1 to ask if reduction of c-kit activity would delay or prevent the development of MPD. Despite a reduction in c-kit activity to approximately 10% of wild-type levels, Nf1-/-;Wv/Wv cells induced MPD in recipient mice. |
