Molecular pathogenesis of multiple myeloma: Basic and clinical updates

Research output: Contribution to journalArticle

78 Scopus citations

Abstract

Multiple myeloma is divided into two distinct genetic subtypes based on chromosome content. Hyperdiploid myeloma is characterized by multiple trisomies of chromosomes 3, 5, 7, 9 11, 15, 19 and 21, and lacks recurrent immunoglobulin gene translocations. Nonhyperdiploid myeloma in contrast is characterized by chromosome translocations t(4;14), t(14;16), t(14;20), t(6;14) and t(11;14). A unifying event in the pathogenesis of multiple myeloma is the dysregulated expression of a cyclin D gene, either directly by juxtaposition to an immunoglobulin enhancer, as a result of ectopic expression of a MAF family transcription factor, or indirectly by as yet unidentified mechanisms. Secondary genetic events include rearrangements of MYC, activating mutations of NRAS, KRAS or BRAF, a promiscuous array of mutations that activate NFkB and deletions of 17p. Among the poor-risk genetic features are t(4;14), t(14;16), t(14;20), del 17p and gains of 1q. Available evidence supports the use of a risk-stratified approach to the treatment of patients with multiple myeloma, with the early and prolonged use of bortezomib particularly in patients with t(4;14) and del 17p.

Original languageEnglish (US)
Pages (from-to)313-323
Number of pages11
JournalInternational journal of hematology
Volume97
Issue number3
DOIs
StatePublished - Mar 2013

Keywords

  • Genetics
  • Multiple myeloma
  • Pathogenesis
  • Prognosis
  • Treatment

ASJC Scopus subject areas

  • Hematology

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