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FLT3 mutations confer enhanced proliferation and survival properties to multipotent progenitors in a murine model of chronic myelomonocytic leukemia.
Lee, Benjamin H; Tothova, Zuzana; Levine, Ross L; Anderson, Kristina; Buza-Vidas, Natalija; Cullen, Dana E; McDowell, Elizabeth P; Adelsperger, Jennifer; Fröhling, Stefan; Huntly, Brian J P; Beran, Miloslav; Jacobsen, Sten Eirik; Gilliland, D Gary.
Afiliação
  • Lee BH; Division of Hematology, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA. bhlee@partners.org
Cancer Cell ; 12(4): 367-80, 2007 Oct.
Article em En | MEDLINE | ID: mdl-17936561
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.
Assuntos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Células-Tronco Hematopoéticas / Leucemia Mielomonocítica Crônica / Células-Tronco Multipotentes / Proliferação de Células / Tirosina Quinase 3 Semelhante a fms / Mutação / Transtornos Mieloproliferativos Tipo de estudo: Prognostic_studies Limite: Animals / Humans Idioma: En Revista: Cancer Cell Ano de publicação: 2007 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Células-Tronco Hematopoéticas / Leucemia Mielomonocítica Crônica / Células-Tronco Multipotentes / Proliferação de Células / Tirosina Quinase 3 Semelhante a fms / Mutação / Transtornos Mieloproliferativos Tipo de estudo: Prognostic_studies Limite: Animals / Humans Idioma: En Revista: Cancer Cell Ano de publicação: 2007 Tipo de documento: Article