Abstract
Several signaling systems downstream of G-CSFR have been identified that are defective or hyperactivated in myeloid cells of patients with congenital neutropenia: severely reduced expression of myeloid-specific transcription factors LEF-1 and C/EBPα, severely reduced expression and functions of HCLS1 protein, severely reduced expression of neutrophil elastase protein, dramatic compensatory up-regulation of the NAMPT/NAD(+)/SIRT pathway leading to continuous activation of emergency granulopoiesis via the transcription factor C/EBPβ, and hyperactivation of STAT5 protein by tyrosine phosphorylation.
Copyright © 2013 Elsevier Inc. All rights reserved.
MeSH terms
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Adaptor Proteins, Signal Transducing / genetics
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Animals
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Blood Proteins / genetics
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CCAAT-Enhancer-Binding Protein-alpha / genetics
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Cell Differentiation / genetics
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Cell Transformation, Neoplastic / genetics
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Cell Transformation, Neoplastic / metabolism
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Gene Expression Regulation
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Humans
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Leukocyte Elastase / genetics
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Lymphoid Enhancer-Binding Factor 1 / genetics
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Mutation
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Myeloid Cells / metabolism
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Myeloid Progenitor Cells / cytology
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Myeloid Progenitor Cells / metabolism
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Myelopoiesis / genetics
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Neutropenia / congenital*
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Neutropenia / genetics*
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Neutropenia / metabolism
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Nicotinamide Phosphoribosyltransferase / metabolism
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Receptors, Granulocyte Colony-Stimulating Factor / deficiency
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Receptors, Granulocyte Colony-Stimulating Factor / genetics*
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Signal Transduction*
Substances
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Adaptor Proteins, Signal Transducing
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Blood Proteins
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CCAAT-Enhancer-Binding Protein-alpha
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HAX1 protein, human
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HCLS1 protein, human
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Lymphoid Enhancer-Binding Factor 1
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Receptors, Granulocyte Colony-Stimulating Factor
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Nicotinamide Phosphoribosyltransferase
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Leukocyte Elastase