Diversity and Diversification of Light Chains in Myeloma:The Specter of Amyloidogenesis by Proxy
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BACKGROUND/AIMS: Primary amyloidosis and the cancer, multiple myeloma, are characterized by the overproduction of free antibody light chains. Approximately 10% of myeloma patients develop amyloidosis; primary amyloidosis may be thought of as the pathological analog of monoclonal gammopathy of undetermined significance. The kidney is a common site of accumulation of amyloid fibrils and is also the target of other light chain pathologies. Understanding the structural origin of these pathologies is complicated by the extreme primary structure heterogeneity of light chains. METHODS: Patterns of light chain germline gene usage in myeloma patients were compared to those found in other immune system disorders: lymphoma, leukemia, systemic lupus erythematosus and rheumatoid arthritis. RESULTS: Significant differences in apparent gene usage are found in the various diseases; several germline gene products have not been documented in myeloma patients to date. CONCLUSION: The plasma cell dyscrasias including myeloma, lymphoma, leukemia, and monoclonal gammopathy of undetermined significance are usually monoclonal diseases; however, the light chains produced are not homogeneous. Thus, the pathological risk for the patient may change during the course of the illness. Mutation rates in light chains observed during clonal diversification parallel mutations occurring in all genes in the malignant cells and could be a clinically useful biomarker.
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