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  • PROTEINS  (2)
  • multiple myeloma  (2)
  • 1
    Keywords: USA ; hematology ; myeloma ; NOV ; MULTIPLE-MYELOMA ; multiple myeloma ; PROTEIN ; PROTEINS ; BLOOD
    Type of Publication: Meeting abstract published
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  • 2
    Keywords: Plasma cells ; D ; A ; PLASMA-CELLS ; MARROW ; methods ; BONE ; GENE ; GENE-EXPRESSION ; GENES ; SAMPLES ; SAMPLE ; PROTEIN ; PROTEINS ; PATIENT ; CELLS ; EXPRESSION ; CELL ; MULTIPLE-MYELOMA ; expression profiling ; OVEREXPRESSION ; DIFFERENTIAL EXPRESSION ; multiple myeloma ; CHROMOSOMES ; DELETION ; score ; IN-SITU ; COPY NUMBER ; AMPLIFICATION ; BONE-MARROW ; affymetrix ; gene expression ; PLASMA ; LOCALIZATION ; PCR ; PATHOGENESIS
    Abstract: Introduction: Multiple myeloma (MM) is proposed to consist of two main pathogenetic groups. While hyperdiploid MM (HD) is characterized by multiple trisomies of odd chromosomes, in non-hyperdiploid MM (NHD), one of the recurrent IgH-translocations and deletion 13 can frequently be found. Aim of this study was to find genes, which discriminate between HD and NHD. Methods: CD138-positive bone marrow plasma cells from 104 patients with previously untreated MM were purified by MACS-sorting. HD and NHD were assigned using a copy number score based on results of interphase fluorescence in situ hybridisation analyses. Gene expression profiling was performed on 40 MM samples with Affymetrix DNA-microarrays. To find genes that discriminate between HD and NHD samples, a two-sided-t-test was done on in a multiple testing procedure, using GCRMA-normalized gene expression values. To validate the identified genes, a publicly available MM gene expression dataset comprising 65 MM patients was used. Expression data of NPM1 was further confirmed by quantitative real-time PCR and western blotting on 64 MM independent samples. In 18 of these samples, the localization of NPM1 was investigated using immunofluorescence. Abstracts Onkologie 2009, 32(suppl 4):1-254 177 Goemans global test was used to test the influence of ribosomal protein gene expression between HD and NHD. Results: Fifty-four genes were significantly differentially expressed between HD and NHD. Nineteen of 47 genes, which were overexpressed in HD, coded for ribosomal proteins. In addition, Nucleophosmin (NPM1) was upregulated in HD. The differential expression of 25 genes, including NPM1 and 13 ribosomal protein genes, was validated with a publicly available gene expression data set of 65 MM patients. The overexpression of NPM1 in HD could be confirmed by quantitative real-time PCR and western blotting. It was the result of an amplification of chromosome 5. NPM1 was localized to the nucleoli of MM cells. Goemans global test showed that HD is associated with an overexpression of ribosomal protein genes, independent of their localization on the trisomic or other chromosomes. Conclusions: Our results indicate that gain of chromosome 5 might play an important role in the pathogenesis of HD.Gemeinsame Jahrestagung der Deutschen, Österreichischen und Schweizerischen Gesellschaften für Hämatologie und Onkologie, 2.-6. Oktober 2009, Heidelberg/Mannheim
    Type of Publication: Meeting abstract published
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