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Publication : Tet2 loss leads to increased hematopoietic stem cell self-renewal and myeloid transformation.

First Author  Moran-Crusio K Year  2011
Journal  Cancer Cell Volume  20
Issue  1 Pages  11-24
PubMed ID  21723200 Mgi Jnum  J:174053
Mgi Id  MGI:5051839 Doi  10.1016/j.ccr.2011.06.001
Citation  Moran-Crusio K, et al. (2011) Tet2 loss leads to increased hematopoietic stem cell self-renewal and myeloid transformation. Cancer Cell 20(1):11-24
abstractText  Somatic loss-of-function mutations in the ten-eleven translocation 2 (TET2) gene occur in a significant proportion of patients with myeloid malignancies. Although there are extensive genetic data implicating TET2 mutations in myeloid transformation, the consequences of Tet2 loss in hematopoietic development have not been delineated. We report here an animal model of conditional Tet2 loss in the hematopoietic compartment that leads to increased stem cell self-renewal in vivo as assessed by competitive transplant assays. Tet2 loss leads to a progressive enlargement of the hematopoietic stem cell compartment and eventual myeloproliferation in vivo, including splenomegaly, monocytosis, and extramedullary hematopoiesis. In addition, Tet2(+/-) mice also displayed increased stem cell self-renewal and extramedullary hematopoiesis, suggesting that Tet2 haploinsufficiency contributes to hematopoietic transformation in vivo.
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