Abstract
STAT5 is activated in a broad spectrum of human hematologic malignancies. We addressed whether STAT5 activation is necessary for the myelo- and lymphoproliferative disease induced by TEL/JAK2 using a genetic approach. Whereas mice transplanted with bone marrow transduced with retrovirus expressing TEL/JAK2 develop a rapidly fatal myelo- and lymphoproliferative syndrome, reconstitution with bone marrow derived from Stat5ab-deficient mice expressing TEL/JAK2 did not induce disease. Disease induction in the Stat5a/b-deficient background was rescued with a bicistronic retrovirus encoding TEL/JAK2 and Stat5a. Furthermore, myeloproliferative disease was induced by reconstitution with bone marrow cells expressing a constitutively active mutant, Stat5a, or a single Stat5a target, murine oncostatin M (mOSM). These data define a critical role for Stat5a/b and mOSM in the pathogenesis of TEL/JAK2 disease.
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.
MeSH terms
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Animals
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Blotting, Southern
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Bone Marrow Cells / pathology
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Bone Marrow Transplantation
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Colony-Forming Units Assay
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DNA, Neoplasm / analysis
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DNA-Binding Proteins / genetics*
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Fibrosis
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Flow Cytometry
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Gene Transfer Techniques
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Lymphoproliferative Disorders / genetics
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Lymphoproliferative Disorders / physiopathology*
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Mice
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Mice, Mutant Strains
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Milk Proteins*
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Mutagenesis / physiology
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Myeloproliferative Disorders / genetics
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Myeloproliferative Disorders / physiopathology*
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Neoplasm Transplantation
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Oncogene Proteins, Fusion / genetics*
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Oncostatin M
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Peptides / genetics
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Phenotype
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Retroviridae / genetics
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STAT5 Transcription Factor
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Trans-Activators / genetics*
Substances
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DNA, Neoplasm
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DNA-Binding Proteins
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Milk Proteins
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OSM protein, human
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Oncogene Proteins, Fusion
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Osm protein, mouse
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Peptides
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STAT5 Transcription Factor
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Stat5a protein, mouse
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TEL-JAK2 fusion protein, human
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TEL-JAK2 fusion protein, mouse
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Trans-Activators
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Oncostatin M