title: STAT1 acts as a tumor promoter for leukemia development.
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.
authors.affiliation: Department of Pharmacology, Medical University of Vienna (MUW), Vienna A-1090, Austria.
authors.forename: Boris
authors.initials: B
authors.lastname: Kovacic
authors.forename: Dagmar
authors.initials: D
authors.lastname: Stoiber
authors.forename: Richard
authors.initials: R
authors.lastname: Moriggl
authors.forename: Eva
authors.initials: E
authors.lastname: Weisz
authors.forename: René G
authors.initials: RG
authors.lastname: Ott
authors.forename: Rita
authors.initials: R
authors.lastname: Kreibich
authors.forename: David E
authors.initials: DE
authors.lastname: Levy
authors.forename: Hartmut
authors.initials: H
authors.lastname: Beug
authors.forename: Michael
authors.initials: M
authors.lastname: Freissmuth
authors.forename: Veronika
authors.initials: V
authors.lastname: Sexl
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002470:Cell Survival / Q000235:genetics; D002471:Cell Transformation, Neoplastic / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D018450:Disease Progression; D005838:Genotype; D015395:Histocompatibility Antigens Class I / Q000276:immunology / Q000378:metabolism; D007371:Interferon-gamma / Q000235:genetics / Q000378:metabolism; D007694:Killer Cells, Natural / Q000276:immunology / Q000378:metabolism; D007942:Leukemia, Experimental / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D016374:Oncogene Proteins v-abl / Q000235:genetics / Q000378:metabolism; D015514:Oncogene Proteins, Fusion / Q000235:genetics / Q000378:metabolism; D010641:Phenotype; D050794:STAT1 Transcription Factor / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D013234:Stem Cells / Q000378:metabolism / Q000473:pathology; D016019:Survival Analysis; D053614:Janus Kinase 2; D000097764:ETS Translocation Variant 6 Protein
chemical_list: D004268:DNA-Binding Proteins; D015395:Histocompatibility Antigens Class I; D007371:Interferon-gamma; D016374:Oncogene Proteins v-abl; D015514:Oncogene Proteins, Fusion; D050794:STAT1 Transcription Factor; C499308:Rag2 protein, mouse; C494080:Stat1 protein, mouse; C491568:TEL-JAK2 fusion protein, mouse; D053614:Janus Kinase 2; D000097764:ETS Translocation Variant 6 Protein