STAT1 acts as a tumor promoter for leukemia development

Cancer Cell. 2006 Jul;10(1):77-87. doi: 10.1016/j.ccr.2006.05.025.

Abstract

The tumor suppressor STAT1 is considered a key regulator of the surveillance of developing tumors. Here, we describe an unexpected tumor-promoting role for STAT1 in leukemia. STAT1(-/-) mice are partially protected from leukemia development, and STAT1(-/-) tumor cells induce leukemia in RAG2(-/-) and immunocompetent mice with increased latency. The low MHC class I protein levels of STAT1(-/-) tumor cells enable efficient NK cell lysis and account for the enhanced tumor clearance. Strikingly, STAT1(-/-) tumor cells acquire increased MHC class I expression upon leukemia progression. These findings define STAT1 as a tumor promoter in leukemia development. Furthermore, we describe the upregulation of MHC class I expression as a general mechanism that allows for the escape of hematopoietic malignancies from immune surveillance.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • B-Lymphocytes / metabolism
  • B-Lymphocytes / pathology
  • Cell Line, Tumor
  • Cell Proliferation
  • Cell Survival / genetics
  • Cell Transformation, Neoplastic / genetics
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism
  • Disease Progression
  • Genotype
  • Histocompatibility Antigens Class I / immunology
  • Histocompatibility Antigens Class I / metabolism
  • Interferon-gamma / genetics
  • Interferon-gamma / metabolism
  • Killer Cells, Natural / immunology
  • Killer Cells, Natural / metabolism
  • Leukemia, Experimental / genetics
  • Leukemia, Experimental / metabolism
  • Leukemia, Experimental / pathology*
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Oncogene Proteins v-abl / genetics
  • Oncogene Proteins v-abl / metabolism
  • Oncogene Proteins, Fusion / genetics
  • Oncogene Proteins, Fusion / metabolism
  • Phenotype
  • STAT1 Transcription Factor / deficiency
  • STAT1 Transcription Factor / genetics
  • STAT1 Transcription Factor / physiology*
  • Stem Cells / metabolism
  • Stem Cells / pathology
  • Survival Analysis

Substances

  • DNA-Binding Proteins
  • Histocompatibility Antigens Class I
  • Oncogene Proteins v-abl
  • Oncogene Proteins, Fusion
  • Rag2 protein, mouse
  • STAT1 Transcription Factor
  • Stat1 protein, mouse
  • TEL-JAK2 fusion protein, mouse
  • Interferon-gamma