Extrinsic signals determine myeloid-erythroid lineage switch in MN1 leukemia Academic Article uri icon

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abstract

  • 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.

authors

  • Heuser, Michael
  • Park, Gyeongsin
  • Moon, Yeonsook
  • Berg, Tobias
  • Xiang, Ping
  • Kuchenbauer, Florian
  • Vollett, Sarah
  • Lai, Courteney
  • Humphries, R Keith

publication date

  • March 2010

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