TET2 Inactivation Results in Pleiotropic Hematopoietic Abnormalities in Mouse and Is a Recurrent Event during Human Lymphomagenesis

被引：728

作者：

Quivoron, Cyril ^{[1
,2
,3
]}

Couronne, Lucile ^{[1
,2
,3
]}

Della Valle, Veronique ^{[1
,2
,3
]}

Lopez, Cecile K. ^{[1
,2
,3
]}

Plo, Isabelle ^{[2
,3
,4
]}

Wagner-Ballon, Orianne ^{[4
,5
]}

Do Cruzeiro, Marcio ^{[6
,7
,8
]}

Delhommeau, Francois ^{[4
,9
]}

Arnulf, Bertrand ^{[10
]}

Stern, Marc-Henri ^{[11
]}

Godley, Lucy ^{[12
]}

Opolon, Paule

Tilly, Herve ^{[13
]}

Solary, Eric ^{[2
,3
,4
]}

Duffourd, Yannis ^{[3
]}

Dessen, Philippe ^{[1
,2
,3
]}

Merle-Beral, Helene ^{[14
,15
,16
]}

Florence Nguyen-Khac ^{[14
,15
,16
]}

Fontenay, Michaela ^{[17
,18
]}

Vainchenker, William ^{[2
,3
,4
]}

Bastard, Christian

Mercher, Thomas ^{[1
,2
,3
]}

Bernard, Olivier A. ^{[1
,2
,3
]}

机构：

[1] INSERM, U985, F-94805 Villejuif, France

[2] Univ Paris 11, F-91400 Orsay, France

[3] Inst Gustave Roussy, F-94805 Villejuif, France

[4] INSERM, U1009, F-94805 Villejuif, France

[5] Hop Henri Mondor, F-94000 Creteil, France

[6] INSERM, U1016, Inst Cochin, F-75014 Paris, France

[7] CNRS, UMR 8104, F-75014 Paris, France

[8] Univ Paris 05, Fac Med Paris Descartes, F-75014 Paris, France

[9] Univ Paris 06, Hop St Antoine, F-75005 Paris, France

[10] Univ Paris 07, Hop St Louis, A 3963, F-75010 Paris, France

[11] Inst Curie, INSERM, U830, F-75005 Paris, France

[12] Univ Chicago, Dept Med, Chicago, IL 60637 USA

[13] Univ Rouen, Ctr Henri Becquerel, INSERM, U918, F-76038 Rouen, France

[14] Hop La Pitie Salpetriere, APHP, Serv Hematol Biol, F-75005 Paris, France

[15] Univ Paris 06, F-75005 Paris, France

[16] INSERM, U872, F-75005 Paris, France

[17] Grp Hosp Broca Cochin Hotel Dieu, AP HP, Serv Hermatol Biol, F-75014 Paris, France

[18] Univ Paris 05, Fac Med Paris Descartes, Inst Cochin, Dept Immunohematol,INSERM,U1016,UMR 8104, F-75014 Paris, France

来源：

CANCER CELL | 2011年 / 20卷 / 01期

关键词：

STEM-CELLS; MYELOPROLIFERATIVE NEOPLASMS; MUTATIONS; 5-HYDROXYMETHYLCYTOSINE; LEUKEMIA; FREQUENT; 5-METHYLCYTOSINE; CONVERSION; COMMON; 4Q24;

D O I：

10.1016/j.ccr.2011.06.003

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

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.

引用

页码：25 / 38

页数：14

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