title: Downregulation of IRS2 in myelodysplastic syndrome: a possible role in impaired hematopoietic cell differentiation.
abstract: Insulin receptor substrate 2 (IRS2) is an adaptor protein that associates with the receptor of erythropoietin, insulin-like growth factor 1 and thrombopoietin; however, its role is not known in myelodysplasia. We, herein, report a significantly lower IRS2 expression in MDS cells, compared to normal cells. IRS2 expression was reduced in high-risk, compared to low-risk disease, and positively correlated with neutrophil and platelet counts. IRS2 was upregulated during erythroid differentiation of CD34(+) cells from normal donors and low-risk MDS patients and also during erythroid, granulocytic and megakaryocytic differentiation in cell lines. These results suggest that defective IRS2 expression plays a role in the impaired hematopoietic cell differentiation in MDS.
authors.affiliation: Hematology and Hemotherapy Center, University of Campinas/Hemocentro-Unicamp, Instituto Nacional de Ciência e Tecnologia do Sangue, Campinas, São Paulo, Brazil.
authors.forename: João Agostinho
authors.initials: JA
authors.lastname: Machado-Neto
authors.forename: Patricia
authors.initials: P
authors.lastname: Favaro
authors.forename: Mariana
authors.initials: M
authors.lastname: Lazarini
authors.forename: Adriana
authors.initials: A
authors.lastname: da Silva Santos Duarte
authors.forename: Leticia Fröhlich
authors.initials: LF
authors.lastname: Archangelo
authors.forename: Irene
authors.initials: I
authors.lastname: Lorand-Metze
authors.forename: Fernando Ferreira
authors.initials: FF
authors.lastname: Costa
authors.forename: Sara Teresinha Olalla
authors.initials: ST
authors.lastname: Saad
authors.forename: Fabiola
authors.initials: F
authors.lastname: Traina
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016022:Case-Control Studies; D002454:Cell Differentiation / Q000235:genetics; D045744:Cell Line, Tumor; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000473:pathology; D015536:Down-Regulation / Q000235:genetics; D015973:Gene Expression Regulation, Leukemic; D006410:Hematopoiesis / Q000235:genetics* / Q000502:physiology; D006412:Hematopoietic Stem Cells / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D055504:Insulin Receptor Substrate Proteins / Q000235:genetics* / Q000502:physiology*; D007938:Leukemia / Q000209:etiology / Q000235:genetics / Q000473:pathology; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000235:genetics* / Q000503:physiopathology; D012307:Risk Factors; D055815:Young Adult
chemical_list: C526297:IRS2 protein, human; D055504:Insulin Receptor Substrate Proteins