The role of TC-PTP (PTPN2) in modulating sensitivity to imatinib and interferon-α in CML cell line, KT-1 cells

Leuk Res. 2013 Sep;37(9):1150-5. doi: 10.1016/j.leukres.2013.05.008. Epub 2013 Jun 4.

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.

Keywords: BCR-ABL; CML (chronic myeloid leukemia); Imatinib; Interferon-α; JAK/STAT; TC-PTP.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antiviral Agents / pharmacology
  • Apoptosis / drug effects
  • Benzamides / pharmacology*
  • Blotting, Western
  • Cell Proliferation / drug effects
  • Drug Resistance, Neoplasm*
  • Fusion Proteins, bcr-abl / antagonists & inhibitors
  • Fusion Proteins, bcr-abl / metabolism
  • Humans
  • Imatinib Mesylate
  • Interferon-alpha / pharmacology*
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / drug therapy*
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / metabolism
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / pathology
  • Phosphorylation / drug effects
  • Piperazines / pharmacology*
  • Protein Kinase Inhibitors / pharmacology
  • Protein Tyrosine Phosphatase, Non-Receptor Type 2 / antagonists & inhibitors
  • Protein Tyrosine Phosphatase, Non-Receptor Type 2 / genetics
  • Protein Tyrosine Phosphatase, Non-Receptor Type 2 / metabolism*
  • Pyrimidines / pharmacology*
  • RNA, Small Interfering / genetics
  • STAT1 Transcription Factor / metabolism*
  • Signal Transduction
  • Tumor Cells, Cultured

Substances

  • Antiviral Agents
  • Benzamides
  • Interferon-alpha
  • Piperazines
  • Protein Kinase Inhibitors
  • Pyrimidines
  • RNA, Small Interfering
  • STAT1 Transcription Factor
  • STAT1 protein, human
  • Imatinib Mesylate
  • Fusion Proteins, bcr-abl
  • PTPN2 protein, human
  • Protein Tyrosine Phosphatase, Non-Receptor Type 2