title: p-ERK1/2 is a predictive factor of response to erythropoiesis-stimulating agents in low/int-1 myelodysplastic syndromes.
abstract: Serum erythropoietin level less than 100U/L and a transfusion requirement of less than 2 units per month are the best predictive factors for response to treatment by erythropoiesis-stimulating agents in low/int-1 myelodysplastic syndromes. To investigate the factors influencing the response to erythropoiesis-stimulating agents, we enrolled 127 low/int-1 myelodysplastic syndrome patients at diagnosis in a biological study of erythropoiesis. The 54 non-responders had a significantly lower number of burst-forming unit-erythroid and colony-forming unit-erythroid than responders. Erythropoietin-dependent proliferation and survival, and phospho (p)-ERK1/2 expression in steady state and after erythropoietin stimulation were defective in cultured erythroblasts. By flow cytometry, p-ERK1/2 was significantly lower in bone marrow CD45(-)/CD71(+)/GPA(-)cells from non-responders compared to responders or controls. Receiver Operator Characteristic curve analysis showed that this flow cytometry test was a sensitive biomarker for predicting the response to erythropoiesis-stimulating agents.
authors.affiliation: Département d’Immunologie-Hématologie, Institut Cochin, INSERM U1016, 3Centre National de la Recherche Scientifique, Paris Cedex 14, France.
authors.forename: Emilie
authors.initials: E
authors.lastname: Frisan
authors.forename: Patrycja
authors.initials: P
authors.lastname: Pawlikowska
authors.forename: Cecile
authors.initials: C
authors.lastname: Pierre-Eugène
authors.forename: Vivian
authors.initials: V
authors.lastname: Viallon
authors.forename: Laure
authors.initials: L
authors.lastname: Gibault
authors.forename: Sophie
authors.initials: S
authors.lastname: Park
authors.forename: Patrick
authors.initials: P
authors.lastname: Mayeux
authors.forename: François
authors.initials: F
authors.lastname: Dreyfus
authors.forename: Françoise
authors.initials: F
authors.lastname: Porteu
authors.forename: Michaëla
authors.initials: M
authors.lastname: Fontenay
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D004900:Erythroblasts / Q000201:enzymology* / Q000473:pathology; D004920:Erythropoiesis / Q000187:drug effects; D004921:Erythropoietin / Q000097:blood / Q000494:pharmacology; D005260:Female; D005434:Flow Cytometry; D015971:Gene Expression Regulation, Enzymologic; D006397:Hematinics / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D019950:Mitogen-Activated Protein Kinase 1 / Q000096:biosynthesis*; D048052:Mitogen-Activated Protein Kinase 3 / Q000096:biosynthesis*; D009190:Myelodysplastic Syndromes / Q000188:drug therapy / Q000201:enzymology* / Q000473:pathology
chemical_list: D015415:Biomarkers; D006397:Hematinics; D004921:Erythropoietin; C535150:MAPK1 protein, human; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3
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