title: Understanding the molecular biology of myeloma and its therapeutic implications.
abstract: Myeloma develops due to the accumulation of multiple pathological genetic events, many of which have been defined. Hyperdiploidy and reciprocal translocations centered on the immunoglobulin heavy chain variable region constitute primary genetic lesions. These primary lesions co-operate with secondary genetic events including chromosomal deletions and gains, gene mutations and epigenetic modifiers such as DNA methylation to produce the malignant phenotype of myeloma. Some of these events have been linked with distinct clinical outcome and can be used to define patient groups. This review explores the molecular biology of myeloma and identifies how genetic lesions can be used to define high- and low-risk patient groups, and also defines potential targets for therapy. The authors also explore how this information can be used to guide therapeutic decision-making and the design and interpretation of clinical trials, both now and in the future.
authors.affiliation: The Institute of Cancer Research, Brookes Lawley Building, 15 Cotswold Road, Sutton, Surrey, UK.
authors.forename: Kevin D
authors.initials: KD
authors.lastname: Boyd
authors.forename: Charlotte
authors.initials: C
authors.lastname: Pawlyn
authors.forename: Gareth J
authors.initials: GJ
authors.lastname: Morgan
authors.forename: Faith E
authors.initials: FE
authors.lastname: Davies
mesh_terms: D002869:Chromosome Aberrations; D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000235:genetics; D008967:Molecular Biology; D009101:Multiple Myeloma / Q000235:genetics* / Q000473:pathology / Q000628:therapy; D011379:Prognosis
chemical_list: D007143:Immunoglobulin Heavy Chains