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http://purl.uniprot.org/citations/12393561http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/12393561http://www.w3.org/2000/01/rdf-schema#comment"Low-risk myelodysplastic syndromes (MDS), including refractory anemia and sideroblastic anemia, are characterized by increased apoptotic death of erythroid progenitors. The signaling pathways that elicit this pathologic cell death in MDS have, however, remained unclear. Treatment with erythropoietin in combination with granulocyte colony-stimulating factor (G-CSF) may synergistically improve the anemia in patients with MDS, with a concomitant decrease in the number of apoptotic bone marrow precursors. Moreover, we have previously reported that G-CSF inhibits Fas-induced caspase activation in sideroblastic anemia (RARS). The present data demonstrate that almost 50% of erythroid progenitor cells derived from patients with MDS exhibit spontaneous release of cytochrome c from mitochondria with ensuing activation of caspase-9, whereas normal erythroid progenitors display neither of these features. G-CSF significantly inhibited cytochrome c release and suppressed apoptosis, most noticeably in cells from patients with sideroblastic anemia. Furthermore, inhibition of caspase-9 suppressed both spontaneous and Fas-mediated apoptosis of erythroid progenitors in all low-risk MDS cases studied. We propose that the increased sensitivity of MDS progenitor cells to death receptor stimulation is due to a constitutive activation of the mitochondrial axis of the apoptotic signaling pathway in these cells. These studies yield a mechanistic explanation for the beneficial clinical effects of growth factor administration in patients with MDS, and provide a model for the study of growth factor-mediated suppression of apoptosis in other bone marrow disorders."xsd:string
http://purl.uniprot.org/citations/12393561http://purl.org/dc/terms/identifier"doi:10.1182/blood-2002-06-1774"xsd:string
http://purl.uniprot.org/citations/12393561http://purl.uniprot.org/core/author"Hellstrom-Lindberg E."xsd:string
http://purl.uniprot.org/citations/12393561http://purl.uniprot.org/core/author"Christensson B."xsd:string
http://purl.uniprot.org/citations/12393561http://purl.uniprot.org/core/author"Zhivotovsky B."xsd:string
http://purl.uniprot.org/citations/12393561http://purl.uniprot.org/core/author"Fadeel B."xsd:string
http://purl.uniprot.org/citations/12393561http://purl.uniprot.org/core/author"Forsblom A.M."xsd:string
http://purl.uniprot.org/citations/12393561http://purl.uniprot.org/core/author"Samuelsson J."xsd:string
http://purl.uniprot.org/citations/12393561http://purl.uniprot.org/core/author"Tehranchi R."xsd:string
http://purl.uniprot.org/citations/12393561http://purl.uniprot.org/core/date"2003"xsd:gYear
http://purl.uniprot.org/citations/12393561http://purl.uniprot.org/core/name"Blood"xsd:string
http://purl.uniprot.org/citations/12393561http://purl.uniprot.org/core/pages"1080-1086"xsd:string
http://purl.uniprot.org/citations/12393561http://purl.uniprot.org/core/title"Granulocyte colony-stimulating factor inhibits spontaneous cytochrome c release and mitochondria-dependent apoptosis of myelodysplastic syndrome hematopoietic progenitors."xsd:string
http://purl.uniprot.org/citations/12393561http://purl.uniprot.org/core/volume"101"xsd:string
http://purl.uniprot.org/citations/12393561http://www.w3.org/2004/02/skos/core#exactMatchhttp://purl.uniprot.org/pubmed/12393561
http://purl.uniprot.org/citations/12393561http://xmlns.com/foaf/0.1/primaryTopicOfhttps://pubmed.ncbi.nlm.nih.gov/12393561
http://purl.uniprot.org/uniprot/#_A0A0B4U5E3-mappedCitation-12393561http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/12393561
http://purl.uniprot.org/uniprot/#_C3VB11-mappedCitation-12393561http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/12393561
http://purl.uniprot.org/uniprot/#_B4DNY7-mappedCitation-12393561http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/12393561
http://purl.uniprot.org/uniprot/#_B4YQS0-mappedCitation-12393561http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/12393561
http://purl.uniprot.org/uniprot/#_D7RVA3-mappedCitation-12393561http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/12393561
http://purl.uniprot.org/uniprot/#_P09919-mappedCitation-12393561http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/12393561
http://purl.uniprot.org/uniprot/#_Q8N4W3-mappedCitation-12393561http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/12393561
http://purl.uniprot.org/uniprot/#_Q5FBY7-mappedCitation-12393561http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/12393561