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 Blood, 1 November 2007, Vol. 110, No. 9, pp. 3112-3121.
Prepublished online as a Blood First Edition Paper on July 18, 2007; DOI 10.1182/blood-2007-02-069625.

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REVIEW IN TRANSLATIONAL HEMATOLOGY

Immunoglobulin gene rearrangements and the pathogenesis of multiple myeloma

David González1, Mirjam van der Burg2, Ramón García-Sanz3, James A. Fenton4, Anton W. Langerak2, Marcos González3, Jacques J. M. van Dongen2, Jesus F. San Miguel3, and Gareth J. Morgan1

1 Section of Haemato-Oncology, Institute of Cancer Research and Royal Marsden Hospital, London, United Kingdom; 2 Immunology Department, Erasmus Medical Center, University Medical Center, Rotterdam, The Netherlands; 3 Haematology Department, Hospital Universitario de Salamanca, Salamanca, Spain; and 4 Department of Haematological Oncology, Leeds University, Leeds, United Kingdom

The ability to rearrange the germ-line 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 protooncogenes 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 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 pathobiology of myeloma.


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