FLT3 mutations confer enhanced proliferation and survival properties to multipotent progenitors in a murine model of chronic myelomonocytic leukemia

Benjamin H. Lee; Zuzana Tothova; Ross L. Levine; Kristina Anderson; Natalija Buza-Vidas; Dana E. Cullen; Elizabeth P. McDowell; Jennifer Adelsperger; Stefan Frhling; Brian J. P. Huntly; Miloslav Beran; Sten Eirik W Jacobsen; D. Gary Gilliland

doi:10.1016/j.ccr.2007.08.031

FLT3 mutations confer enhanced proliferation and survival properties to multipotent progenitors in a murine model of chronic myelomonocytic leukemia

Benjamin H. Lee, Zuzana Tothova, Ross L. Levine, Kristina Anderson, Natalija Buza-Vidas, Dana E. Cullen, Elizabeth P. McDowell, Jennifer Adelsperger, Stefan Frhling, Brian J. P. Huntly, Miloslav Beran, Sten Eirik W Jacobsen, D. Gary Gilliland

Stem Cell Center

Research output: Contribution to journal › Article › peer-review

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.

Original language	English
Pages (from-to)	367-380
Journal	Cancer Cell
Volume	12
Issue number	4
DOIs	https://doi.org/10.1016/j.ccr.2007.08.031
Publication status	Published - 2007

Subject classification (UKÄ)

Cancer and Oncology

UN SDGs

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10.1016/j.ccr.2007.08.031

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Lee, B. H., Tothova, Z., Levine, R. L., Anderson, K., Buza-Vidas, N., Cullen, D. E., McDowell, E. P., Adelsperger, J., Frhling, S., Huntly, B. J. P., Beran, M., Jacobsen, S. E. W., & Gilliland, D. G. (2007). FLT3 mutations confer enhanced proliferation and survival properties to multipotent progenitors in a murine model of chronic myelomonocytic leukemia. Cancer Cell, 12(4), 367-380. https://doi.org/10.1016/j.ccr.2007.08.031

@article{d3267e343a2c4baf98493c6b0af601c2,

title = "FLT3 mutations confer enhanced proliferation and survival properties to multipotent progenitors in a murine model of chronic myelomonocytic leukemia",

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 Zuzana Tothova and Levine, {Ross L.} and Kristina Anderson and Natalija Buza-Vidas and Cullen, {Dana E.} and McDowell, {Elizabeth P.} and Jennifer Adelsperger and Stefan Frhling and Huntly, {Brian J. P.} and Miloslav Beran and Jacobsen, {Sten Eirik W} and Gilliland, {D. Gary}",

year = "2007",

doi = "10.1016/j.ccr.2007.08.031",

language = "English",

volume = "12",

pages = "367--380",

journal = "Cancer Cell",

issn = "1878-3686",

publisher = "Cell Press",

number = "4",

}

Lee, BH, Tothova, Z, Levine, RL, Anderson, K, Buza-Vidas, N, Cullen, DE, McDowell, EP, Adelsperger, J, Frhling, S, Huntly, BJP, Beran, M, Jacobsen, SEW & Gilliland, DG 2007, 'FLT3 mutations confer enhanced proliferation and survival properties to multipotent progenitors in a murine model of chronic myelomonocytic leukemia', Cancer Cell, vol. 12, no. 4, pp. 367-380. https://doi.org/10.1016/j.ccr.2007.08.031

TY - JOUR

T1 - FLT3 mutations confer enhanced proliferation and survival properties to multipotent progenitors in a murine model of chronic myelomonocytic leukemia

AU - Lee, Benjamin H.

AU - Tothova, Zuzana

AU - Levine, Ross L.

AU - Anderson, Kristina

AU - Buza-Vidas, Natalija

AU - Cullen, Dana E.

AU - McDowell, Elizabeth P.

AU - Adelsperger, Jennifer

AU - Frhling, Stefan

AU - Huntly, Brian J. P.

AU - Beran, Miloslav

AU - Jacobsen, Sten Eirik W

AU - Gilliland, D. Gary

PY - 2007

Y1 - 2007

N2 - 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.

AB - 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.

U2 - 10.1016/j.ccr.2007.08.031

DO - 10.1016/j.ccr.2007.08.031

M3 - Article

C2 - 17936561

SN - 1878-3686

VL - 12

SP - 367

EP - 380

JO - Cancer Cell

JF - Cancer Cell

IS - 4

ER -

FLT3 mutations confer enhanced proliferation and survival properties to multipotent progenitors in a murine model of chronic myelomonocytic leukemia

Abstract

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UN SDGs

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