Deletion of the protein tyrosine phosphatase gene PTPN2 in T-cell acute lymphoblastic leukemia

被引：143

作者：

Kleppe, Maria ^{[3
,4
]}

Lahortiga, Idoya ^{[3
,4
]}

El Chaar, Tiama ^{[1
,2
]}

De Keersmaecker, Kim ^{[3
,4
,5
]}

Mentens, Nicole ^{[3
,4
]}

Graux, Carlos ^{[6
]}

Van Roosbroeck, Katrien ^{[3
,4
]}

Ferrando, Adolfo A. ^{[5
,7
,8
]}

Langerak, Anton W. ^{[9
]}

Meijerink, Jules P. P. ^{[10
]}

Sigaux, Francois ^{[1
,2
]}

Haferlach, Torsten ^{[11
]}

Wlodarska, Iwona ^{[4
]}

Vandenberghe, Peter ^{[4
]}

Soulier, Jean ^{[1
,2
]}

Cools, Jan ^{[3
,4
]}

机构：

[1] INSERM, U944, Paris, France

[2] Hop St Louis, Hematol Lab, Inst Univ Hematol, Paris, France

[3] VIB, Dept Mol & Dev Genet, Louvain, Belgium

[4] Katholieke Univ Leuven, Ctr Human Genet, Louvain, Belgium

[5] Columbia Univ, Med Ctr, Inst Canc Genet, New York, NY USA

[6] Clin Univ Mt Godinne, Yvoir, Belgium

[7] Columbia Univ, Dept Pathol, Med Ctr, New York, NY USA

[8] Columbia Univ, Dept Pediat, Med Ctr, New York, NY 10027 USA

[9] Erasmus MC, Dept Immunol, Rotterdam, Netherlands

[10] Erasmus Med Ctr Sophia, Dept Pediat, Rotterdam, Netherlands

[11] Munich Leukemia Lab, Munich, Germany

来源：

NATURE GENETICS | 2010年 / 42卷 / 06期

基金：

美国国家卫生研究院; 欧洲研究理事会;

关键词：

MOLECULAR PATHOGENESIS; ACTIVATION; IDENTIFICATION; TRANSLOCATION; REGULATOR; FUSION; ABL1;

D O I：

10.1038/ng.587

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

PTPN2 (protein tyrosine phosphatase non-receptor type 2, also known as TC-PTP) is a cytosolic tyrosine phosphatase that functions as a negative regulator of a variety of tyrosine kinases and other signaling proteins(1-3). In agreement with its role in the regulation of the immune system, PTPN2 was identified as a susceptibility locus for autoimmune diseases(4,5). In this work, we describe the identification of focal deletions of PTPN2 in human T-cell acute lymphoblastic leukemia (T-ALL). Deletion of PTPN2 was specifically found in T-ALLs with aberrant expression of the TLX1 transcription factor oncogene(6), including four cases also expressing the NUP214-ABL1 tyrosine kinase(7). Knockdown of PTPN2 increased the proliferation and cytokine sensitivity of T-ALL cells. In addition, PTPN2 was identified as a negative regulator of NUP214-ABL1 kinase activity. Our study provides genetic and functional evidence for a tumor suppressor role of PTPN2 and suggests that expression of PTPN2 may modulate response to treatment.

引用

页码：530 / U84

页数：8