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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 | 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

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Associated grants

  • Agency: NCI NIH HHS, United States
    Id: CA66996
  • Agency: NCI NIH HHS, United States
    Id: CA113434
  • Agency: NCI NIH HHS, United States
    Id: CA105423
  • Agency: NCI NIH HHS, United States
    Id: P01 CA066996
  • Agency: Medical Research Council, United Kingdom
    Id: G116/187
  • Agency: PHS HHS, United States
    Id: HHMI_GILLILAND_D
  • Agency: NCI NIH HHS, United States
    Id: P01 CA066996-100001
  • Agency: NCI NIH HHS, United States
    Id: K08 CA113434-02
  • Agency: NCI NIH HHS, United States
    Id: U01 CA105423
  • Agency: NCI NIH HHS, United States
    Id: K08 CA113434-01A1
  • Agency: NCI NIH HHS, United States
    Id: K08 CA113434
  • Agency: Howard Hughes Medical Institute, United States

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Mutation Surveyor (tool)

RRID:SCR_001247

THIS RESOURCE IS NO LONGER IN SERVICE. Documented on September 23,2022. Software for DNA sequencing analysis that integates with Sanger Sequencing files generated by Applied Biosystems Genetic Analyzers, MegaBACE, and Beckman CEQ electrophoresis systems. It can be used to find single nucleotide polymorphisms (SNPs), insertions and deletions (INDELS), and somatic mutations in direct sequencing, PCR sequencing, mitochondrial DNA sequencing, and resequencing projects.

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