Identification of primary MAFB target genes in multiple myeloma

Esther van Stralen, Marc van de Wetering, Luca Agnelli, Antonino Neri, Hans C. Clevers, Bert J E G Bast

Research output: Contribution to journalArticle

Abstract

Objective: In multiple myeloma (MM), seven primary recurrent translocations involving the immunoglobulin heavy chain locus have been identified. One of the partner loci maps to 20q12 and involves the MAFB gene resulting in its ectopic expression. We attempt here to identify MAFB target genes in MM. Materials and Methods: We used an inducible system to upregulate MAFB in MM cell lines not carrying the t(14;20). Microarray expression analysis was used to detect gene expression changes upon MAFB expression. These genes were further evaluated comparatively with gene expression profiles obtained from MM or plasma cell leukemia tumors carrying an activated MAFB gene. Functional implications of these upregulated genes were studied by testing their promoter activity in reporter assays. C-MAF was included comparatively as well. Results: The inducible cell lines identified a total of 284 modulated transcripts. After further evaluation using ex vivo data 14 common upregulated genes were found, common to the C-MAF pathway as well. The promoter activity of some of these secondary genes proved a functional relationship with MAFB. In connection with one of these secondary genes (NOTCH2), even tertiary upregulated genes were found. Functional studies indicated that inducible MAFB expression conferred antiapoptotic effects. Conclusion: We identified 14 upregulated genes, and their downstream consequences in the combined MAFB/C-MAF pathway. Eleven of these genes are novel in the C-MAF pathway as well. These direct target genes may be responsible for the oncogenic transformation of MAF expressing myeloma cells.

Original languageEnglish
Pages (from-to)78-86
Number of pages9
JournalExperimental Hematology
Volume37
Issue number1
DOIs
Publication statusPublished - Jan 2009

Fingerprint

Multiple Myeloma
Genes
Plasma Cell Leukemia
Cell Line
Immunoglobulin Heavy Chains
Plasmacytoma
Microarray Analysis
Transcriptome
Up-Regulation
Gene Expression

ASJC Scopus subject areas

  • Cancer Research
  • Cell Biology
  • Genetics
  • Molecular Biology
  • Hematology

Cite this

Identification of primary MAFB target genes in multiple myeloma. / van Stralen, Esther; van de Wetering, Marc; Agnelli, Luca; Neri, Antonino; Clevers, Hans C.; Bast, Bert J E G.

In: Experimental Hematology, Vol. 37, No. 1, 01.2009, p. 78-86.

Research output: Contribution to journalArticle

van Stralen, Esther ; van de Wetering, Marc ; Agnelli, Luca ; Neri, Antonino ; Clevers, Hans C. ; Bast, Bert J E G. / Identification of primary MAFB target genes in multiple myeloma. In: Experimental Hematology. 2009 ; Vol. 37, No. 1. pp. 78-86.
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