Preparing your results

Our searching services are busy right now. Your search will reload in five seconds.

Forgot Password

If you have forgotten your password you can enter your email here and get a temporary password sent to your email.

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

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.

Pubmed ID: 17936561


  • Lee BH
  • Tothova Z
  • Levine RL
  • Anderson K
  • Buza-Vidas N
  • Cullen DE
  • McDowell EP
  • Adelsperger J
  • Fröhling S
  • Huntly BJ
  • Beran M
  • Jacobsen SE
  • Gilliland DG


Cancer cell

Publication Data

October 15, 2007

Associated Grants

  • Agency: NCI NIH HHS, Id: CA105423
  • Agency: NCI NIH HHS, Id: CA113434
  • Agency: NCI NIH HHS, Id: CA66996
  • Agency: Medical Research Council, Id: G116/187
  • Agency: NCI NIH HHS, Id: K08 CA113434-01A1
  • Agency: NCI NIH HHS, Id: K08 CA113434-02
  • Agency: NCI NIH HHS, Id: P01 CA066996
  • Agency: NCI NIH HHS, Id: P01 CA066996-100001

Mesh Terms

  • Animals
  • Cell Differentiation
  • Cell Proliferation
  • Cell Survival
  • Cells, Cultured
  • Exons
  • Gene Expression Regulation, Neoplastic
  • Genotype
  • Hematopoietic Stem Cells
  • Humans
  • Kaplan-Meier Estimate
  • Leukemia, Experimental
  • Leukemia, Myelomonocytic, Chronic
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Multipotent Stem Cells
  • Mutation
  • Myeloproliferative Disorders
  • Phenotype
  • Signal Transduction
  • fms-Like Tyrosine Kinase 3