Tet2 loss leads to increased hematopoietic stem cell self-renewal and myeloid transformation.
Tet2 loss leads to increased hematopoietic stem cell self-renewal and myeloid transformation.
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DOI：
10.1016/j.ccr.2011.06.001
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发表时间：
2011-07-12
期刊：
影响因子：
50.3
通讯作者：
Levine RL
中科院分区：
文献类型：
--
作者：
Moran-Crusio K;Reavie L;Shih A;Abdel-Wahab O;Ndiaye-Lobry D;Lobry C;Figueroa ME;Vasanthakumar A;Patel J;Zhao X;Perna F;Pandey S;Madzo J;Song C;Dai Q;He C;Ibrahim S;Beran M;Zavadil J;Nimer SD;Melnick A;Godley LA;Aifantis I;Levine RL
10 - 11易位-2 （TET2）基因的体细胞功能丧失突变发生在很大比例的髓系恶性肿瘤患者中。尽管有大量的遗传数据表明TET2突变与髓细胞转化有关，但造血室中TET2丢失的后果尚未明确。我们在此报告了一个动物模型，在造血室条件Tet2丢失，导致增加干细胞自我更新在体内通过竞争性移植试验评估。Tet2缺失导致造血干细胞室进行性增大，最终导致体内骨髓增生，包括脾肿大、单核细胞增多和髓外造血。此外，Tet2+/−小鼠也表现出干细胞自我更新和髓外造血的增加，这表明Tet2单倍体不足有助于体内造血转化。
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 the hematopoietic compartment have not been delineated. We report here an animal model of conditional Tet2 loss in the hematopoietic compartment which 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 extramedulary hematopoiesis, suggesting Tet2 haploinsufficiency contributes to hematopoietic transformation in vivo.
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影响因子：
11.2
作者：
Abdel-Wahab O;Manshouri T;Patel J;Harris K;Yao J;Hedvat C;Heguy A;Bueso-Ramos C;Kantarjian H;Levine RL;Verstovsek S
通讯作者：
Verstovsek S
影响因子：
64.8
作者：
通讯作者：
--
影响因子：
50.3
作者：
Figueroa ME;Abdel-Wahab O;Lu C;Ward PS;Patel J;Shih A;Li Y;Bhagwat N;Vasanthakumar A;Fernandez HF;Tallman MS;Sun Z;Wolniak K;Peeters JK;Liu W;Choe SE;Fantin VR;Paietta E;Löwenberg B;Licht JD;Godley LA;Delwel R;Valk PJ;Thompson CB;Levine RL;Melnick A
通讯作者：
Melnick A
影响因子：
30.8
作者：
Langemeijer, Saskia M. C.;Kuiper, Roland P.;Jansen, Joop H.
通讯作者：
Jansen, Joop H.
体细胞突变改变生发中心起源的滤泡性和弥漫性大 B 细胞淋巴瘤中的 EZH2 (Tyr641)。
影响因子：
30.8
作者：
Morin, Ryan D.;Johnson, Nathalie A.;Severson, Tesa M.;Mungall, Andrew J.;An, Jianghong;Goya, Rodrigo;Paul, Jessica E.;Boyle, Merrill;Woolcock, Bruce W.;Kuchenbauer, Florian;Yap, Damian;Humphries, R. Keith;Griffith, Obi L.;Shah, Sohrab;Zhu, Henry;Kimbara, Michelle;Shashkin, Pavel;Charlot, Jean F.;Tcherpakov, Marianna;Corbett, Richard;Tam, Angela;Varhol, Richard;Smailus, Duane;Moksa, Michelle;Zhao, Yongjun;Delaney, Allen;Qian, Hong;Birol, Inanc;Schein, Jacqueline;Moore, Richard;Holt, Robert;Horsman, Doug E.;Connors, Joseph M.;Jones, Steven;Aparicio, Samuel;Hirst, Martin;Gascoyne, Randy D.;Marra, Marco A.
通讯作者：
Marra, Marco A.