Abstract:
: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.
journal_name
Cancer Celljournal_title
Cancer cellauthors
Moran-Crusio K,Reavie L,Shih A,Abdel-Wahab O,Ndiaye-Lobry D,Lobry C,Figueroa ME,Vasanthakumar A,Patel J,Zhao X,Perna F,Pandey S,Madzo J,Song C,Dai Q,He C,Ibrahim S,Beran M,Zavadil J,Nimer SD,Melnick A,Godley LAdoi
10.1016/j.ccr.2011.06.001subject
Has Abstractpub_date
2011-07-12 00:00:00pages
11-24issue
1eissn
1535-6108issn
1878-3686pii
S1535-6108(11)00222-4journal_volume
20pub_type
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