Journal
BLOOD
Volume 117, Issue 26, Pages 7090-7098Publisher
AMER SOC HEMATOLOGY
DOI: 10.1182/blood-2010-10-314286
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Funding
- Fonds voor Wetenschappelijk Onderzoek (National Fund for Scientific Research)-Vlaanderen [G.0287.07]
- Foundation against Cancer [SCIE2006-34]
- European Research Council
- Katholieke Universiteit Leuven
- Federal Office for Scientific, Technical and Cultural Affairs, Belgium
- French program Carte d'Identite des Tumeurs (Ligue Contre le Cancer)
- Canceropole d'Ile de France
- Associazione Italiana per la Ricerca sul Cancro [IG 2009-8803]
- Actions de Recherche Concertees
- Communaute Francaise de Belgique
- Direction de la Recherche Scientifique [ARC 09/14-021]
- association Laurette Fugain
- regional committee of the Ligue contre le Cancer,
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We have recently reported inactivation of the tyrosine phosphatase PTPN2 (also known as TC-PTP) through deletion of the entire gene locus in similar to 6% of T-cell acute lymphoblastic leukemia (T-ALL) cases. T-ALL is an aggressive disease of the thymocytes characterized by the step-wise accumulation of chromosomal abnormalities and gene mutations. In the present study, we confirmed the strong association of the PTPN2 deletion with TLX1 and NUP214-ABL1 expression. In addition, we found cooperation between PTPN2 deletion and activating JAK1 gene mutations. Activating mutations in JAK1 kinase occur in similar to 10% of human T-ALL cases, and aberrant kinase activity has been shown to confer proliferation and survival advantages. Our results reveal that some JAK1 mutation-positive T-ALLs harbor deletions of the tyrosine phosphatase PTPN2, a known negative regulator of the JAK/STAT pathway. We provide evidence that down-regulation of Ptpn2 sensitizes lymphoid cells to JAK1-mediated transformation and reduces their sensitivity to JAK inhibition. (Blood. 2011;11(26):7090-7098)
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