FLT3 mutations confer enhanced proliferation and survival properties to multipotent progenitors in a murine model of chronic myelomonocytic leukemia

Research output: Contribution to journalArticle

Abstract

Despite their known transforming properties, the effects of leukemogenic FLT3-ITD mutations on hematopoietic stem and multipotent progenitor cells and on hematopoietic differentiation are not well understood. We report a mouse model harboring an ITD in the murine Flt3 locus that develops myeloproliferative disease resembling CMML and further identified FLT3-ITD mutations in a subset of human CMML. These findings correlated with an increase in number, cell cycling, and survival of multipotent stem and progenitor cells in an ITD dose-dependent manner in animals that exhibited alterations within their myeloid progenitor compartments and a block in normal B cell development. This model provides insights into the consequences of constitutive signaling by an oncogenic tyrosine kinase on hematopoietic progenitor quiescence, function, and cell fate.

Details

Authors
  • Benjamin H. Lee
  • Zuzana Tothova
  • Ross L. Levine
  • Kristina Anderson
  • Natalija Buza-Vidas
  • Dana E. Cullen
  • Elizabeth P. McDowell
  • Jennifer Adelsperger
  • Stefan Frhling
  • Brian J. P. Huntly
  • Miloslav Beran
  • Sten Eirik W Jacobsen
  • D. Gary Gilliland
Organisations
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Cancer and Oncology
Original languageEnglish
Pages (from-to)367-380
JournalCancer Cell
Volume12
Issue number4
Publication statusPublished - 2007
Publication categoryResearch
Peer-reviewedYes