| First Author | Heuser M | Year | 2010 |
| Journal | Exp Hematol | Volume | 38 |
| Issue | 3 | Pages | 174-9 |
| PubMed ID | 20096329 | Mgi Jnum | J:158349 |
| Mgi Id | MGI:4438641 | Doi | 10.1016/j.exphem.2010.01.003 |
| Citation | Heuser M, et al. (2010) Extrinsic signals determine myeloid-erythroid lineage switch in MN1 leukemia. Exp Hematol 38(3):174-9 |
| abstractText | OBJECTIVE: Transcriptional control of hematopoietic lineage fate relies on the integration of many intra- and extracellular signals. To test whether the microenvironment impacts on leukemic phenotype, we exploited the MN1 model of acute myeloid leukemia under defined genetically modified microenvironmental conditions. MATERIALS AND METHODS: The requirement of both FLT3 and c-Kit signaling for MN1 leukemias was investigated using retroviral infection of bone marrow cells from wild-type, c-Kit-mutated (W41), and Flt3-ligand knockout cells, and bone marrow transplantation into wild-type, c-Kit-mutated, or Flt3-ligand knockout mice. RESULTS: Genetic disruption of both FLT3 and c-Kit signaling in the MN1-leukemia model was dispensable for MN1-induced leukemogenesis. However, it induced a switch from myeloid to erythroid phenotype that was preserved, when FLT3 signaling was restored by secondary transplantation of leukemic cells into wild-type recipients. CONCLUSIONS: Our findings underscore the importance of microenvironmental signals for lineage choice in leukemia and identify signals that are important in myeloid-erythroid lineage decisions. |
