Abstract
Signal transducer and activator of transcription (STAT) proteins are a 7-member family of cytoplasmic transcription factors that contribute to signal transduction by cytokines, hormones, and growth factors. STAT proteins control fundamental cellular processes, including survival, proliferation, and differentiation. Given the critical roles of STAT proteins, it was hypothesized that inappropriate or aberrant activation of STATs might contribute to cellular transformation and, in particular, leukemogenesis. Constitutive activation of mutated STAT3 has in fact been demonstrated to result in transformation. STAT activation has been extensively studied in leukemias, and mechanisms of STAT activation and the potential role of STAT signaling in leukemogenesis are the focus of this review. A better understanding of mechanisms of dysregulation of STAT signaling pathways may serve as a basis for designing novel therapeutic strategies that target these pathways in leukemia cells.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
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Review
MeSH terms
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Animals
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Antineoplastic Agents / pharmacology
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Cell Differentiation
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DNA-Binding Proteins / antagonists & inhibitors
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DNA-Binding Proteins / chemistry
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DNA-Binding Proteins / classification
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DNA-Binding Proteins / genetics
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DNA-Binding Proteins / physiology*
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Drug Design
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Forecasting
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Fusion Proteins, bcr-abl / physiology
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Gene Expression Regulation, Leukemic*
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Granulocyte Colony-Stimulating Factor / physiology
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Humans
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Janus Kinase 2
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Leukemia / genetics
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Leukemia / metabolism*
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Mice
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Mice, Knockout
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Milk Proteins*
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Myeloid Cells / cytology
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Myeloid Cells / metabolism
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Neoplasm Proteins / antagonists & inhibitors
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Neoplasm Proteins / chemistry
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Neoplasm Proteins / genetics
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Neoplasm Proteins / physiology*
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Neoplasms / genetics
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Neoplasms / metabolism
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Oncogene Proteins, Fusion / genetics
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Oncogene Proteins, Fusion / physiology
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Protein Isoforms / chemistry
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Protein Isoforms / genetics
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Protein Isoforms / physiology
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Protein-Tyrosine Kinases / genetics
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Protein-Tyrosine Kinases / physiology
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Proto-Oncogene Proteins*
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STAT3 Transcription Factor
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STAT5 Transcription Factor
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STAT6 Transcription Factor
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Signal Transduction*
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Structure-Activity Relationship
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Trans-Activators / antagonists & inhibitors
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Trans-Activators / classification
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Trans-Activators / genetics
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Trans-Activators / physiology*
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Transcriptional Activation*
Substances
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Antineoplastic Agents
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DNA-Binding Proteins
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Milk Proteins
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Neoplasm Proteins
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Oncogene Proteins, Fusion
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Protein Isoforms
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Proto-Oncogene Proteins
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STAT3 Transcription Factor
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STAT3 protein, human
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STAT5 Transcription Factor
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STAT6 Transcription Factor
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STAT6 protein, human
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Stat3 protein, mouse
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Stat6 protein, mouse
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Trans-Activators
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Granulocyte Colony-Stimulating Factor
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Protein-Tyrosine Kinases
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Fusion Proteins, bcr-abl
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JAK2 protein, human
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Jak2 protein, mouse
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Janus Kinase 2