期刊
NATURE GENETICS
卷 42, 期 6, 页码 530-U84出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/ng.587
关键词
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资金
- K.U. Leuven
- FWO-Vlaanderen [G.0287.07]
- Foundation against Cancer [SCIE2006-34]
- European Research Council
- European Hematology Association
- Federal Office for Scientific, Technical and Cultural Affairs, Belgium
- French program Carte d'Identite des Tumeurs
- Canceropole d'Ile de France
- New York Community Trust
- National Institutes of Health [CA120196, CA129382]
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.
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