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

被引：185

作者：

Lee, Benjamin H. ^{[1
]}

Tothova, Zuzana

Levine, Ross L.

Anderson, Kristina

Buza-Vidas, Natalija

Cullen, Dana E.

McDowell, Elizabeth P.

Adelsperger, Jennifer

Frhling, Stefan

Huntly, Brian J. P.

Beran, Miloslav

Jacobsen, Sten Eirik

Gilliland, D. Gary

机构：

[1] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Med,Div Hematol, Boston, MA 02115 USA

[2] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA

[3] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA

[4] Harvard Univ, Sch Med, Howard Hughes Med Inst, Boston, MA 02115 USA

[5] Lund Univ, Lund Stem Cell Ctr, Hematopoiet Stem Cell Lab, S-22184 Lund, Sweden

[6] Univ Texas, MD Anderson Canc Ctr, Dept Leukemia, Houston, TX 77030 USA

来源：

CANCER CELL | 2007年 / 12卷 / 04期

基金：

英国医学研究理事会;

关键词：

D O I：

10.1016/j.ccr.2007.08.031

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

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.

引用

页码：367 / 380

页数：14

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