title: The role of TC-PTP (PTPN2) in modulating sensitivity to imatinib and interferon-α in CML cell line, KT-1 cells.
abstract: T-cell protein tyrosine phosphatase (TC-PTP, also known as PTPN2) is a negative regulator of the JAK/STAT pathway. STAT5 is activated by BCR-ABL kinase and STAT1 is an important transcription factor for interferon (IFN)-α-induced signaling in chronic myeloid leukemia (CML). We used siRNA to delete TC-PTP in the CML cell line, KT-1, and examined changes in the sensitivity to imatinib and IFN-α. Suppression of TC-PTP induced activation of STAT5, leading to imatinib resistance, while prolonged phosphorylation of STAT1 was induced by IFN-α, triggering cell death in KT-1 cells. These findings suggest that TC-PTP modulates sensitivity to imatinib and IFN-α in CML.
authors.affiliation: Division of Hematology, Keio University School of Medicine, Tokyo, Japan.
authors.forename: Yuriko
authors.initials: Y
authors.lastname: Nishiyama-Fujita
authors.forename: Takatsune
authors.initials: T
authors.lastname: Shimizu
authors.forename: Morihiko
authors.initials: M
authors.lastname: Sagawa
authors.forename: Hideo
authors.initials: H
authors.lastname: Uchida
authors.forename: Masahiro
authors.initials: M
authors.lastname: Kizaki
mesh_terms: D000998:Antiviral Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D001549:Benzamides / Q000494:pharmacology*; D015153:Blotting, Western; D049109:Cell Proliferation / Q000187:drug effects; D019008:Drug Resistance, Neoplasm; D016044:Fusion Proteins, bcr-abl / Q000037:antagonists & inhibitors / Q000378:metabolism; D006801:Humans; D000068877:Imatinib Mesylate; D016898:Interferon-alpha / Q000494:pharmacology*; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D010766:Phosphorylation / Q000187:drug effects; D010879:Piperazines / Q000494:pharmacology*; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D054578:Protein Tyrosine Phosphatase, Non-Receptor Type 2 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D011743:Pyrimidines / Q000494:pharmacology*; D034741:RNA, Small Interfering / Q000235:genetics; D050794:STAT1 Transcription Factor / Q000378:metabolism*; D015398:Signal Transduction; D014407:Tumor Cells, Cultured
chemical_list: D000998:Antiviral Agents; D001549:Benzamides; D016898:Interferon-alpha; D010879:Piperazines; D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D034741:RNA, Small Interfering; D050794:STAT1 Transcription Factor; C494079:STAT1 protein, human; D000068877:Imatinib Mesylate; D016044:Fusion Proteins, bcr-abl; C516649:PTPN2 protein, human; D054578:Protein Tyrosine Phosphatase, Non-Receptor Type 2
keywords: BCR-ABL; CML (chronic myeloid leukemia); Imatinib; Interferon-α; JAK/STAT; TC-PTP