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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 LU ; Buza-Vidas, Natalija LU ; Cullen, Dana E.; McDowell, Elizabeth P.; Adelsperger, Jennifer; Frhling, Stefan and Huntly, Brian J. P., et al. (2007) In Cancer Cell 12(4). p.367-380
Abstract
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... (More)
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. (Less)
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Contribution to journal
publication status
published
subject
in
Cancer Cell
volume
12
issue
4
pages
367 - 380
publisher
Cell Press
external identifiers
  • wos:000250362600010
  • scopus:35048848955
ISSN
1878-3686
DOI
10.1016/j.ccr.2007.08.031
language
English
LU publication?
yes
id
d3267e34-3a2c-4baf-9849-3c6b0af601c2 (old id 654162)
date added to LUP
2007-12-14 13:47:37
date last changed
2017-11-12 03:32:47
@article{d3267e34-3a2c-4baf-9849-3c6b0af601c2,
  abstract     = {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.},
  author       = {Lee, Benjamin H. and Tothova, Zuzana and Levine, Ross L. and Anderson, Kristina and Buza-Vidas, Natalija and Cullen, Dana E. and McDowell, Elizabeth P. and Adelsperger, Jennifer and Frhling, Stefan and Huntly, Brian J. P. and Beran, Miloslav and Jacobsen, Sten Eirik W and Gilliland, D. Gary},
  issn         = {1878-3686},
  language     = {eng},
  number       = {4},
  pages        = {367--380},
  publisher    = {Cell Press},
  series       = {Cancer Cell},
  title        = {FLT3 mutations confer enhanced proliferation and survival properties to multipotent progenitors in a murine model of chronic myelomonocytic leukemia},
  url          = {http://dx.doi.org/10.1016/j.ccr.2007.08.031},
  volume       = {12},
  year         = {2007},
}