Author/Authors :
Quivoron، نويسنده , , Cyril and Couronné، نويسنده , , Lucile and Della Valle، نويسنده , , Véronique and Lopez، نويسنده , , Cécile K. and Plo، نويسنده , , Isabelle and Wagner-Ballon، نويسنده , , Orianne and Do Cruzeiro، نويسنده , , Marcio and Delhommeau، نويسنده , , Francois and Arnulf، نويسنده , , Bertrand and Stern، نويسنده , , Marc-Henri and Godley، نويسنده , , Lucy and Opolon، نويسنده , , Paule and Tilly، نويسنده , , Hervé and Solary، نويسنده , , Eric and Duffourd، نويسنده , , Yannis and Dessen، نويسنده , , Philippe and Merle-Beral، نويسنده , , Hélène and Nguyen-Khac، نويسنده , , Florence and Fontenay، نويسنده , , Michaëla and Vainchenker، نويسنده , , William and Bastard، نويسنده , , Christian and Mercher، نويسنده , , Thomas and Bernard، نويسنده , , Olivier A.، نويسنده ,
Abstract :
Summary
f-function mutations affecting one or both copies of the Ten-Eleven-translocation (TET)2 gene have been described in various human myeloid malignancies. We report that inactivation of Tet2 in mouse perturbs both early and late steps of hematopoiesis including myeloid and lymphoid differentiation in a cell-autonomous manner, endows the cells with competitive advantage, and eventually leads to the development of malignancies. We subsequently observed TET2 mutations in human lymphoid disorders. TET2 mutations could be detected in immature progenitors endowed with myeloid colony-forming potential. Our results show that the mutations present in lymphoid tumor cells may occur at both early and later steps of lymphoid development and indicate that impairment of TET2 function or/and expression predisposes to the development of hematological malignancies.
