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.

Keywords::

• genetics
• myeloma
• prognosis
• risk
• targeted therapy
• therapy

Financial & competing interests disclosure

KD Boyd has been involved in Celgene speaker bureaus. C Pawlyn has received conference travel support from Novartis, Celgene and Janssen. FE Davies is a Cancer Research UK Senior Cancer Fellow. FE Davies and GJ Morgan have been involved in speaker bureaus and advisory boards for Johnson and Johnson, Celgene and Novartis. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.