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

Cancer cell | Oct 15, 2007

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 RIS Download

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

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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

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