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Diversity and diversification of light chains in myeloma: the specter of amyloidogenesis by proxy.
Contrib Nephrol. 2007; 153:156-81.CN

Abstract

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.

Authors+Show Affiliations

Biosciences Division, Argonne National Laboratory, Argonne, IL 60439, USA.No affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, U.S. Gov't, Non-P.H.S.
Review

Language

eng

PubMed ID

17075229

Citation

Gu, Minyi, et al. "Diversity and Diversification of Light Chains in Myeloma: the Specter of Amyloidogenesis By Proxy." Contributions to Nephrology, vol. 153, 2007, pp. 156-81.
Gu M, Wilton R, Stevens FJ. Diversity and diversification of light chains in myeloma: the specter of amyloidogenesis by proxy. Contrib Nephrol. 2007;153:156-81.
Gu, M., Wilton, R., & Stevens, F. J. (2007). Diversity and diversification of light chains in myeloma: the specter of amyloidogenesis by proxy. Contributions to Nephrology, 153, 156-81.
Gu M, Wilton R, Stevens FJ. Diversity and Diversification of Light Chains in Myeloma: the Specter of Amyloidogenesis By Proxy. Contrib Nephrol. 2007;153:156-81. PubMed PMID: 17075229.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Diversity and diversification of light chains in myeloma: the specter of amyloidogenesis by proxy. AU - Gu,Minyi, AU - Wilton,Rosemary, AU - Stevens,Fred J, PY - 2006/11/1/pubmed PY - 2007/1/11/medline PY - 2006/11/1/entrez SP - 156 EP - 81 JF - Contributions to nephrology JO - Contrib Nephrol VL - 153 N2 - 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. SN - 0302-5144 UR - https://www.unboundmedicine.com/medline/citation/17075229/Diversity_and_diversification_of_light_chains_in_myeloma:_the_specter_of_amyloidogenesis_by_proxy_ L2 - https://www.karger.com?DOI=10.1159/000096766 DB - PRIME DP - Unbound Medicine ER -