title: TET2 inactivation results in pleiotropic hematopoietic abnormalities in mouse and is a recurrent event during human lymphomagenesis.
abstract: Loss-of-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.
authors: INSERM, U, Villejuif, France.
authors: Cyril
authors: C
authors: Quivoron
authors: Lucile
authors: L
authors: Couronné
authors: Véronique
authors: V
authors: Della Valle
authors: Cécile K
authors: CK
authors: Lopez
authors: Isabelle
authors: I
authors: Plo
authors: Orianne
authors: O
authors: Wagner-Ballon
authors: Marcio
authors: M
authors: Do Cruzeiro
authors: Francois
authors: F
authors: Delhommeau
authors: Bertrand
authors: B
authors: Arnulf
authors: Marc-Henri
authors: MH
authors: Stern
authors: Lucy
authors: L
authors: Godley
authors: Paule
authors: P
authors: Opolon
authors: Hervé
authors: H
authors: Tilly
authors: Eric
authors: E
authors: Solary
authors: Yannis
authors: Y
authors: Duffourd
authors: Philippe
authors: P
authors: Dessen
authors: Hélène
authors: H
authors: Merle-Beral
authors: Florence
authors: F
authors: Nguyen-Khac
authors: Michaëla
authors: M
authors: Fontenay
authors: William
authors: W
authors: Vainchenker
authors: Christian
authors: C
authors: Bastard
authors: Thomas
authors: T
authors: Mercher
authors: Olivier A
authors: OA
authors: Bernard
mesh_terms: D000818:Animals; D018952:Antigens, CD34 / Q000378:metabolism; D019070:Cell Lineage; D004268:DNA-Binding Proteins / Q000235:genetics*; D049308:Dioxygenases; D020868:Gene Silencing; D006410:Hematopoiesis; D006412:Hematopoietic Stem Cells / Q000378:metabolism / Q000473:pathology; D006706:Homeostasis; D006801:Humans; D008223:Lymphoma / Q000378:metabolism / Q000473:pathology*; D051379:Mice; D023421:Models, Animal; D009154:Mutation / Q000235:genetics; D022423:Myeloid Cells / Q000378:metabolism / Q000473:pathology; D011230:Precancerous Conditions / Q000378:metabolism / Q000473:pathology*; D011518:Proto-Oncogene Proteins / Q000235:genetics*
chemical_list: D018952:Antigens, CD34; D004268:DNA-Binding Proteins; D011518:Proto-Oncogene Proteins; D049308:Dioxygenases; C541081:TET2 protein, human; C551914:Tet2 protein, mouse