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Title: PTPN2 negatively regulates oncogenic JAK1 in T-cell acute lymphoblastic leukemia
Authors: Kleppe, Ria
Soulier, Jean
Asnafi, Vahid
Mentens, Nicole
Hornakova, Tekla
Knoops, Laurent
Constantinescu, Stefan
Sigaux, François
Meijerink, Jules P
Vandenberghe, Peter
Tartaglia, Marco
Foa, Robin
Macintyre, Elizabeth
Haferlach, Torsten
Cools, Jan # ×
Issue Date: May-2011
Publisher: W.B. Saunders
Series Title: Blood vol:117 issue:26 pages:7090-7098
Abstract: We have recently reported inactivation of the tyrosine phosphatase PTPN2 (also known as TC-PTP) through deletion of the entire gene locus in about 6% of T-cell acute lymphoblastic leukemias (T-ALL). T-ALL is an aggressive disease of the thymocytes and characterized by the stepwise accumulation of chromosomal abnormalities and gene mutations. In this work we confirm the strong association of PTPN2 deletion with TLX1 and NUP214-ABL1 expression. In addition, we identify cooperation of PTPN2 deletion with activating JAK1 gene mutations. Activating mutations in the JAK1 kinase occur in about 10% of human T-ALL, and aberrant kinase activity has been shown to confer proliferation and survival advantages. Our current work shows that part of JAK1 mutation-positive T-ALL harbor deletions of the tyrosine phosphatase PTPN2, a known negative regulator of the JAK/STAT pathway. We provide evidence that downregulation of Ptpn2 sensitizes lymphoid cells to JAK1 mediated transformation and reduces their sensitivity to JAK inhibition.
URI: 
ISSN: 0006-4971
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Department of Human Genetics - miscellaneous
Laboratory of Molecular Biology of Leukemia
× corresponding author
# (joint) last author

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