Cookies on this website

We use cookies to ensure that we give you the best experience on our website. If you click 'Accept all cookies' we'll assume that you are happy to receive all cookies and you won't see this message again. If you click 'Reject all non-essential cookies' only necessary cookies providing core functionality such as security, network management, and accessibility will be enabled. Click 'Find out more' for information on how to change your cookie settings.

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.

Original publication




Journal article


Cancer Cell

Publication Date





367 - 380


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