STAT1 acts as a tumor promoter for leukemia development.
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.
Kovacic
Boris
B
Department of Pharmacology, Medical University of Vienna (MUW), Vienna A-1090, Austria.
Stoiber
Dagmar
D
Moriggl
Richard
R
Weisz
Eva
E
Ott
René G
RG
Kreibich
Rita
R
Levy
David E
DE
Beug
Hartmut
H
Freissmuth
Michael
M
Sexl
Veronika
V
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
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