PTPN2 negatively regulates oncogenic JAK1 in T-cell acute lymphoblastic leukemia

Maria Kleppe, Jean Soulier, Vahid Asnafi, Nicole Mentens, Tekla Hornakova, Laurent Knoops, Stefan Constantinescu, François Sigaux, Jules P. Meijerink, Peter Vandenberghe, Marco Tartaglia, Robin Foa, Elizabeth Macintyre, Torsten Haferlach, Jan Cools

Research output: Contribution to journalArticle

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Abstract

We have recently reported inactivation of the tyrosine phosphatase PTPN2 (also known as TC-PTP) through deletion of the entire gene locus in ∼ 6% of T-cell acute lymphoblastic leukemia (T-ALL) cases. T-ALL is an aggressive disease of the thymocytes characterized by the stepwise 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 ∼ 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 TALLs 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.

Original languageEnglish
Pages (from-to)7090-7098
Number of pages9
JournalBlood
Volume117
Issue number26
DOIs
Publication statusPublished - Jun 30 2011

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Precursor T-Cell Lymphoblastic Leukemia-Lymphoma
T-cells
Genes
Phosphoric Monoester Hydrolases
Mutation
Tyrosine
Non-Receptor Type 2 Protein Tyrosine Phosphatase
Phosphotransferases
Ports and harbors
Gene Deletion
Thymocytes
Chromosome Aberrations
Down-Regulation
Lymphocytes
Survival

ASJC Scopus subject areas

  • Hematology
  • Biochemistry
  • Cell Biology
  • Immunology

Cite this

Kleppe, M., Soulier, J., Asnafi, V., Mentens, N., Hornakova, T., Knoops, L., ... Cools, J. (2011). PTPN2 negatively regulates oncogenic JAK1 in T-cell acute lymphoblastic leukemia. Blood, 117(26), 7090-7098. https://doi.org/10.1182/blood-2010-10-314286

PTPN2 negatively regulates oncogenic JAK1 in T-cell acute lymphoblastic leukemia. / Kleppe, Maria; 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.

In: Blood, Vol. 117, No. 26, 30.06.2011, p. 7090-7098.

Research output: Contribution to journalArticle

Kleppe, M, Soulier, J, Asnafi, V, Mentens, N, Hornakova, T, Knoops, L, Constantinescu, S, Sigaux, F, Meijerink, JP, Vandenberghe, P, Tartaglia, M, Foa, R, Macintyre, E, Haferlach, T & Cools, J 2011, 'PTPN2 negatively regulates oncogenic JAK1 in T-cell acute lymphoblastic leukemia', Blood, vol. 117, no. 26, pp. 7090-7098. https://doi.org/10.1182/blood-2010-10-314286
Kleppe M, Soulier J, Asnafi V, Mentens N, Hornakova T, Knoops L et al. PTPN2 negatively regulates oncogenic JAK1 in T-cell acute lymphoblastic leukemia. Blood. 2011 Jun 30;117(26):7090-7098. https://doi.org/10.1182/blood-2010-10-314286
Kleppe, Maria ; 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. / PTPN2 negatively regulates oncogenic JAK1 in T-cell acute lymphoblastic leukemia. In: Blood. 2011 ; Vol. 117, No. 26. pp. 7090-7098.
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