Abstract
Activation of Stat5 is frequently found in leukemias. To study the mechanism and role of Stat5 activation, we introduced a constitutively activated Stat5a mutant, cS5F, into murine bone marrow (BM) cells. BM transplantation with cS5F-transfected cells caused development of multilineage leukemias in lethally irradiated wild-type or nonirradiated Rag2(-/-) mice. The leukemic cells showed strongly enhanced levels of cS5F tetramers but unchanged cS5F dimer levels in a DNA binding assay. Moreover, Stat5a mutants engineered to form only dimers, but not tetramers, failed to induce leukemias. In addition, Stat5 tetramers were found to accumulate in excess compared to dimers in various human leukemias. These data suggest that Stat5 tetramers are associated with leukemogenesis.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Biomarkers
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Bone Marrow Cells / cytology
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Bone Marrow Cells / physiology
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Bone Marrow Transplantation
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Cell Lineage
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Cell Transformation, Neoplastic
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Cells, Cultured
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DNA-Binding Proteins / chemistry*
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DNA-Binding Proteins / genetics
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DNA-Binding Proteins / metabolism*
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Female
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Genetic Complementation Test
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Growth Substances / metabolism
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Humans
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Leukemia / genetics
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Leukemia / metabolism*
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Leukemia / pathology
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Liver / metabolism
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Liver / pathology
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Male
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Mice
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Mice, Knockout
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Milk Proteins / chemistry*
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Milk Proteins / genetics
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Milk Proteins / metabolism*
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Mutation
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Nuclear Proteins
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Oncogenes
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Protein Structure, Quaternary*
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STAT5 Transcription Factor
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Spleen / metabolism
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Spleen / pathology
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Trans-Activators / chemistry*
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Trans-Activators / genetics
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Trans-Activators / metabolism*
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Transfection
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Tumor Suppressor Proteins
Substances
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Biomarkers
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DNA-Binding Proteins
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Growth Substances
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Milk Proteins
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Nuclear Proteins
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RAG2 protein, human
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Rag2 protein, mouse
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STAT5 Transcription Factor
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STAT5A protein, human
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Stat5a protein, mouse
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Trans-Activators
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Tumor Suppressor Proteins
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V(D)J recombination activating protein 2