Author/Authors :
Lee، نويسنده , , Benjamin H. and Tothova، نويسنده , , Zuzana and Levine، نويسنده , , Ross L. and Anderson، نويسنده , , Kristina and Buza-Vidas، نويسنده , , Natalija and Cullen، نويسنده , , Dana E. and McDowell، نويسنده , , Elizabeth P. and Adelsperger، نويسنده , , Jennifer and Frِhling، نويسنده , , Stefan and Huntly، نويسنده , , Brian J.P. and Beran، نويسنده , , Miloslav and Jacobsen، نويسنده , , Sten Eirik and Gilliland، نويسنده , , D. Gary، نويسنده ,
Abstract :
Summary
e 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.
