Abstract
Early B cell development depends on a network of transcription factors, whereby E2A and EBF1 regulate B cell specification and Pax5 controls B-lineage commitment. In contrast, activation of the transcription factor STAT5 in response to IL-7R signaling promotes cell survival by activating the prosurvival gene Mcl1 and orders immunoglobulin gene rearrangement by repressing Igk recombination in pro-B cells. Subsequently, it cooperates with the pre-B cell receptor to facilitate pre-B cell expansion. STAT5 also plays a key role in the generation of B cell precursor acute lymphoblastic leukemia, whereby the BCR-ABL1 translocation or the collaboration of JAK2 mutations with overexpression of the thymic stromal lymphopoietin receptor CRLF2 results in constitutive STAT5 activation leading to cytokine-independent survival and growth of leukemic cells.
Copyright 2010 Elsevier Ltd. All rights reserved.
Publication types
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Research Support, Non-U.S. Gov't
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Review
MeSH terms
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Animals
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B-Lymphocytes / immunology*
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Cell Proliferation
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Cell Survival / genetics
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Cell Survival / immunology
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Fusion Proteins, bcr-abl / genetics
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Fusion Proteins, bcr-abl / metabolism
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Gene Expression Regulation, Developmental* / genetics
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Gene Expression Regulation, Developmental* / immunology
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Gene Expression Regulation, Leukemic* / genetics
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Gene Expression Regulation, Leukemic* / immunology
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Humans
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Interleukin-7 / immunology
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Lymphopoiesis / genetics
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Myeloid Cell Leukemia Sequence 1 Protein
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Precursor Cell Lymphoblastic Leukemia-Lymphoma / genetics
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Precursor Cell Lymphoblastic Leukemia-Lymphoma / immunology*
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Proto-Oncogene Proteins c-bcl-2 / genetics
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Proto-Oncogene Proteins c-bcl-2 / metabolism
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STAT5 Transcription Factor / immunology*
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Signal Transduction / genetics
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Signal Transduction / immunology
Substances
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Interleukin-7
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Myeloid Cell Leukemia Sequence 1 Protein
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Proto-Oncogene Proteins c-bcl-2
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STAT5 Transcription Factor
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Fusion Proteins, bcr-abl