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  • Title: Identification of defects in the transcriptional program during lineage-specific in vitro differentiation of CD34(+) cells selected from patients with both low- and high-risk myelodysplastic syndrome.
    Author: Gueller S, Komor M, Nowak D, Baldus CD, de Vos S, Hoelzer D, Ottmann OG, Hofmann WK.
    Journal: Exp Hematol; 2010 Sep; 38(9):718-32, 732.e1-6. PubMed ID: 20621626.
    Abstract:
    OBJECTIVE: Development of myelodysplastic syndrome (MDS) is suggested to follow a multistep pathogenesis and is characterized by accumulation of molecular defects of the hematopoietic stem/progenitor cells, resulting in aberrant differentiation and proliferation. MATERIALS AND METHODS: To detect alterations within the transcriptional program in MDS-derived CD34(+) cells during lineage-specific differentiation, we performed serial gene expression analysis of in vitro differentiated erythro-, granulo-, and megakaryopoietic cells using oligonucleotide microarrays (HG-U133A, Affymetrix, Santa Clara, CA, USA). For selected genes, expression data were confirmed using real-time polymerase chain reaction. RESULTS: We identified genes with altered expression during lineage-specific differentiation in either low- or high-risk MDS cells compared to the expression patterns of continuously up- or downregulated genes from the normal transcriptional program of hematopoiesis. In cluster analyses, we could show that MDS samples have a distinct expression pattern of a set of selected genes compared to normal cells, which allows prediction of the affiliation of a sample to one group. Furthermore, this study gives an overview of genes that are differentially expressed in MDS cells compared to normal hematopoiesis. CONCLUSION: Our data provide the first comprehensive transcriptional analysis of differentiating human CD34(+) cells derived from MDS patients compared to normal individuals. It gives new insights into the alteration of differentiation and proliferation of MDS stem cells.
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