Tet2 Loss Leads to Increased Hematopoietic Stem Cell Self-Renewal and Myeloid Transformation

被引：1036

作者：

Moran-Crusio, Kelly ^{[2
]}

Reavie, Linsey ^{[2
]}

Shih, Alan ^{[3
,4
]}

Abdel-Wahab, Omar ^{[3
,4
]}

Ndiaye-Lobry, Delphine ^{[2
]}

Lobry, Camille ^{[2
]}

Figueroa, Maria E. ^{[5
]}

Vasanthakumar, Aparna ^{[6
]}

Patel, Jay ^{[3
]}

Zhao, Xinyang ^{[7
]}

Perna, Fabiana ^{[7
]}

Pandey, Suveg ^{[3
]}

Madzo, Jozef ^{[6
]}

Song, Chunxiao ^{[8
,9
]}

Dai, Qing ^{[8
,9
]}

He, Chuan ^{[8
,9
]}

Ibrahim, Sherif

Beran, Miloslav ^{[10
]}

Zavadil, Jiri ^{[1
,11
]}

Nimer, Stephen D. ^{[4
,7
]}

Melnick, Ari ^{[5
]}

Godley, Lucy A. ^{[6
]}

Aifantis, Iannis ^{[1
,2
]}

Levine, Ross L. ^{[3
,4
]}

机构：

[1] NYU, Sch Med, Dept Pathol, NYU Canc Inst, New York, NY 10016 USA

[2] NYU, Sch Med, Howard Hughes Med Inst, New York, NY 10016 USA

[3] Mem Sloan Kettering Canc Ctr, Human Oncol & Pathogenesis Program, New York, NY 10016 USA

[4] Mem Sloan Kettering Canc Ctr, Leukemia Serv, Dept Med, New York, NY 10016 USA

[5] Weill Cornell Med Coll, Div Hematol Oncol, New York, NY 10016 USA

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

[7] Sloan Kettering Inst, Mol Pharmacol & Chem Program, New York, NY 10016 USA

[8] Univ Chicago, Dept Chem, Chicago, IL 60637 USA

[9] Univ Chicago, Inst Biophys Dynam, Chicago, IL 60637 USA

[10] MD Anderson Med Ctr, Dept Leukemia, Houston, TX 77030 USA

[11] NYU Langone Med Ctr, Ctr Hlth Informat & Bioinformat, New York, NY 10016 USA

来源：

CANCER CELL | 2011年 / 20卷 / 01期

基金：

美国国家卫生研究院;

关键词：

METHYLTRANSFERASE GENE EZH2; MYELOPROLIFERATIVE NEOPLASMS; SOMATIC MUTATIONS; MYELODYSPLASTIC SYNDROMES; IDH2; MUTATIONS; IN-VIVO; LEUKEMIA; 5-HYDROXYMETHYLCYTOSINE; MALIGNANCIES; 5-METHYLCYTOSINE;

D O I：

10.1016/j.ccr.2011.06.001

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Somatic 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.

引用

页码：11 / 24

页数：14

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