Submitted February 16, 2007
Accepted July 9, 2007
Immunoglobulin gene rearrangements and the pathogenesis of multiple myeloma
David Gonzalez, Mirjam van der Burg, Ramon Garcia-Sanz, James A. Fenton, Anton W Langerak, Marcos Gonzalez, Jacques J.M. van Dongen, Jesus F. San Miguel, and Gareth J Morgan*
Section of Haemato-Oncology, The Institute of Cancer Research & The Royal Marsden NHS Hospital, London, United Kingdom
Immunology Department, Erasmus MC, University Medical Center, Rotterdam, Netherlands
Haematology Department, Hospital Universitario de Salamanca, Salamanca, Spain
Haematological Oncology, University of Leeds, Leeds, United Kingdom
* Corresponding author; email: gareth.morgan{at}icr.ac.uk.
The ability to rearrange the germline DNA to generate antibody diversity is an essential prerequisite for the production of a functional repertoire. While this is essential to prevent infections, it also represents the "Achilles heal" of the B-cell lineage, occasionally leading to malignant transformation of these cells by translocation of proto-oncogenes into the immunoglobulin (Ig) loci. However, in evolutionary terms this is a small price to pay for a functional immune system. The study of the configuration and rearrangements of the Ig gene loci has contributed extensively to our understanding of the natural history of development of the Myeloma. In addition to this, the analysis of Ig gene rearrangements in B-cell neoplasms provides information about the clonal origin of the disease, prognosis, as well as providing a clinical useful tool for clonality detection and minimal residual disease monitoring. Herein, we review the data currently available on both Ig gene rearrangements and protein patterns seen in Myeloma with the aim of illustrating how this knowledge has contributed to our understanding of the patho-biology of Myeloma.
