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Aberrant gene promoter methylation marking disease progression in multiple myeloma

Leukemia volume 20, pages 1190–1192 (2006)Cite this article

The pathogenesis of multiple myeloma (MM), a neoplastic proliferation of monoclonal plasma cells, is a multi-step process with progressive acquisition of genetic aberrations.1 Disease initiation involves the activation of oncogenes such as D-type cyclins by chromosomal translocations involving the immunoglobulin (Ig) gene. Inactivation of tumor suppressor genes, however, appears to be a late event.1 Clinically, the disease may progress through monoclonal gammopathy of undetermined significance, smouldering myeloma, MM and plasma cell leukemia.

DNA methylation involves the addition of a methyl group to the carbon 5 position of the cytosine ring. Aberrant methylation in the CpG dinucleotide regions of gene promoters results in transcription repression, and may act as an alternative mechanism of gene inactivation.2, 3 In myeloma, aberrant methylation is a frequent genetic alteration that results in perturbation of signaling pathways.4, 5 For instance, we had shown previously that aberrant methylation of SHP1 was associated with absent SHP1 expression, resulting in constitutive activation of the Jak/STAT pathway. Demethylation with 5-azacytidine led to re-expression of SHP1 and downregulation of Jak/STAT signalling, thus demonstrating that aberrant methylation was biologically relevant.4

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Authors and Affiliations

  1. University Department of Medicine, Queen Mary Hospital, Hong Kong, Hong Kong

    C-S Chim, R Liang, M-H Leung, S-F Yip & Y-L Kwong

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  1. C-S Chim
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  2. R Liang
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  5. Y-L Kwong
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Correspondence to Y-L Kwong.

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Chim, CS., Liang, R., Leung, MH. et al. Aberrant gene promoter methylation marking disease progression in multiple myeloma. Leukemia 20, 1190–1192 (2006). https://doi.org/10.1038/sj.leu.2404205

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