Author/Authors :
Moran-Crusio، نويسنده , , Kelly and Reavie، نويسنده , , Linsey and Shih، نويسنده , , Alan and Abdel-Wahab، نويسنده , , Omar and Ndiaye-Lobry، نويسنده , , Delphine and Lobry، نويسنده , , Camille and Figueroa، نويسنده , , Maria E. and Vasanthakumar، نويسنده , , Aparna and Patel، نويسنده , , Jay and Zhao، نويسنده , , Xinyang and Perna، نويسنده , , Fabiana and Pandey، نويسنده , , Suveg and Madzo، نويسنده , , Jozef and Song، نويسنده , , Chunxiao and Dai، نويسنده , , Qing and He، نويسنده , , Chuan and Ibrahim، نويسنده , , Sherif and Beran، نويسنده , , Miloslav and Zavadil، نويسنده , , Jiri and Nimer، نويسنده , , Stephen D. and Melnick، نويسنده , , Ari and Godley، نويسنده , , Lucy A. and Aifantis، نويسنده , , Iannis and Levine، نويسنده , , Ross L.، نويسنده ,
Abstract :
Summary
c 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.
