TY - JOUR
T1 - TET2 Inactivation Results in Pleiotropic Hematopoietic Abnormalities in Mouse and Is a Recurrent Event during Human Lymphomagenesis
AU - Quivoron, Cyril
AU - Couronné, Lucile
AU - Della Valle, Véronique
AU - Lopez, Cécile K.
AU - Plo, Isabelle
AU - Wagner-Ballon, Orianne
AU - Do Cruzeiro, Marcio
AU - Delhommeau, Francois
AU - Arnulf, Bertrand
AU - Stern, Marc Henri
AU - Godley, Lucy
AU - Opolon, Paule
AU - Tilly, Hervé
AU - Solary, Eric
AU - Duffourd, Yannis
AU - Dessen, Philippe
AU - Merle-Beral, Hélène
AU - Nguyen-Khac, Florence
AU - Fontenay, Michaëla
AU - Vainchenker, William
AU - Bastard, Christian
AU - Mercher, Thomas
AU - Bernard, Olivier A.
N1 - Funding Information:
We thank Dr. R. L. Levine and Omar Abdel-Wahab for valuable help with resequencing, Dr. Paola Rivera-Munhoz and Dr. Sophie Ezine for helpful discussions, and Olivia Bawa for histopathological analysis. The work was funded by grants from INSERM, Institut National du Cancer (INCa), Ligue Nationale Contre le Cancer (LNCC), Association de Recherche contre le Cancer (ARC), Fondation Gustave Roussy and by NIH/NCI grants CA129831 and CA129831-03S1 (L.G.). C.Q. is the recipient of a fellowship from the region île de France.
PY - 2011/7/12
Y1 - 2011/7/12
N2 - 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.
AB - 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.
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U2 - 10.1016/j.ccr.2011.06.003
DO - 10.1016/j.ccr.2011.06.003
M3 - Article
C2 - 21723201
AN - SCOPUS:79960062301
SN - 1535-6108
VL - 20
SP - 25
EP - 38
JO - Cancer cell
JF - Cancer cell
IS - 1
ER -