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

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Kleppe, Maria Lahortiga, Idoya El Chaar, Tiama De Keersmaecker, Kim Mentens, Nicole Graux, Carlos [MGD] Cools, Jan

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. In agreement with its role in the regulation of the immune system, PTPN2 was identified as a susceptibility locus for autoimmune diseases. 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, including four cases also expressing the NUP214-ABL1 tyrosine kinase. 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.

Document type Article de périodique (Journal article) – Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't
Access type Accès mixte
Publication date 2010
Language Anglais
Journal information "Nature Genetics" - Vol. 42, no. 6, p. 530-535 (2010)
Peer reviewed yes
Publisher Nature Publishing Group ((United States) New York)
issn 1061-4036
e-issn 1546-1718
Publication status Publié
Affiliations UCL - (MGD) Service d'hématologie
UCL - SSS/IREC/MONT - Pôle Mont Godinne
MESH Subject Animals ; Cell Line ; Leukemia, Experimental - genetics ; Mice ; Piperazines - therapeutic use ; Precursor T-Cell Lymphoblastic Leukemia-Lymphoma - genetics ; Protein Tyrosine Phosphatase, Non-Receptor Type 2 - genetics ; Proto-Oncogene Proteins - genetics ; Pyrimidines - therapeutic use ; Cell Line, Tumor ; Chemokine CCL1 - metabolism ; Gene Deletion ; Gene Knockdown Techniques ; Homeodomain Proteins - genetics ; Humans ; Interleukin-2 - metabolism ; Interleukin-7 - metabolism
Links
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Bibliographic reference Kleppe, Maria ; Lahortiga, Idoya ; El Chaar, Tiama ; De Keersmaecker, Kim ; Mentens, Nicole ; et. al. Deletion of the protein tyrosine phosphatase gene PTPN2 in T-cell acute lymphoblastic leukemia.. In: Nature Genetics, Vol. 42, no. 6, p. 530-535 (2010)
Permanent URL http://hdl.handle.net/2078.1/109935