西亚试剂：Deletion of the protein tyrosine phosphatase gene PTPN2 in

Deletion of the protein tyrosine phosphatase gene PTPN2 in T-cell acute lymphoblastic leukemia
Maria Kleppe1,2, Idoya Lahortiga1,2, Tiama El Chaar3, Kim De Keersmaecker1,2,4, Nicole Mentens1,2, Carlos Graux5, Katrien Van Roosbroeck1,2, Adolfo A Ferrando4,6,7, Anton W Langerak8, Jules P P Meijerink9, Fran?ois Sigaux3, Torsten Haferlach10, Iwona Wlodarska2, Peter Vandenberghe2, Jean Soulier3 & Jan Cools1,2

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 proteins1, 2, 3. In agreement with its role in the regulation of the immune system, PTPN2 was identified as a susceptibility locus for autoimmune diseases4, 5. 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 oncogene6, including four cases also expressing the NUP214-ABL1 tyrosine kinase7. 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.

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