STAT1 acts as a tumor promoter for leukemia development

Boris Kovacic, Dagmar Stoiber, Richard Moriggl, Eva Weisz, René G Ott, Rita Kreibich, David E Levy, Hartmut Beug, Michael Freissmuth, Veronika Sexl

Research output: Journal article (peer-reviewed)Journal article

122 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)77-87
Number of pages11
JournalCancer Cell
Volume10
Issue number1
DOIs
Publication statusPublished - Jul 2006
Externally publishedYes

Keywords

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

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