title: Deletion of the protein tyrosine phosphatase gene PTPN2 in T-cell acute lymphoblastic leukemia.
abstract: 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.
authors.affiliation: Department of Molecular and Developmental Genetics, VIB, Leuven, Belgium.
authors.forename: Maria
authors.initials: M
authors.lastname: Kleppe
authors.forename: Idoya
authors.initials: I
authors.lastname: Lahortiga
authors.forename: Tiama
authors.initials: T
authors.lastname: El Chaar
authors.forename: Kim
authors.initials: K
authors.lastname: De Keersmaecker
authors.forename: Nicole
authors.initials: N
authors.lastname: Mentens
authors.forename: Carlos
authors.initials: C
authors.lastname: Graux
authors.forename: Katrien
authors.initials: K
authors.lastname: Van Roosbroeck
authors.forename: Adolfo A
authors.initials: AA
authors.lastname: Ferrando
authors.forename: Anton W
authors.initials: AW
authors.lastname: Langerak
authors.forename: Jules P P
authors.initials: JP
authors.lastname: Meijerink
authors.forename: François
authors.initials: F
authors.lastname: Sigaux
authors.forename: Torsten
authors.initials: T
authors.lastname: Haferlach
authors.forename: Iwona
authors.initials: I
authors.lastname: Wlodarska
authors.forename: Peter
authors.initials: P
authors.lastname: Vandenberghe
authors.forename: Jean
authors.initials: J
authors.lastname: Soulier
authors.forename: Jan
authors.initials: J
authors.lastname: Cools
mesh_terms: D000818:Animals; D001549:Benzamides; D002460:Cell Line; D045744:Cell Line, Tumor; D054402:Chemokine CCL1 / Q000378:metabolism; D017353:Gene Deletion; D055785:Gene Knockdown Techniques; D018398:Homeodomain Proteins / Q000235:genetics; D006801:Humans; D000068877:Imatinib Mesylate; D007376:Interleukin-2 / Q000378:metabolism; D015851:Interleukin-7 / Q000378:metabolism; D007942:Leukemia, Experimental / Q000235:genetics; D051379:Mice; D010879:Piperazines / Q000627:therapeutic use; D054218:Precursor T-Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics*; D054578:Protein Tyrosine Phosphatase, Non-Receptor Type 2 / Q000235:genetics*; D011518:Proto-Oncogene Proteins / Q000235:genetics; D011743:Pyrimidines / Q000627:therapeutic use
chemical_list: D001549:Benzamides; D054402:Chemokine CCL1; D018398:Homeodomain Proteins; D007376:Interleukin-2; D015851:Interleukin-7; D010879:Piperazines; D011518:Proto-Oncogene Proteins; D011743:Pyrimidines; C071250:TLX1 protein, human; D000068877:Imatinib Mesylate; C516649:PTPN2 protein, human; D054578:Protein Tyrosine Phosphatase, Non-Receptor Type 2
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