Contributions to Nephrology 2006
DOI: 10.1159/000096766
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Diversity and Diversification of Light Chains in Myeloma:The Specter of Amyloidogenesis by Proxy

Abstract: 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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Cited by 6 publications
(3 citation statements)
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“…This set is composed of LCs from other PCDs, not only from MM ( n = 152) but also from LCDD ( n = 7) and WM ( n = 4). Although LCDD sequences by definition do not form fibrils [25], it is possible that some of the MM sequences could be amyloidogenic, as up to 10–20% of MM cases can develop fibrillar LC deposits [2628]; thus, it is possible that some of the sequences classified as MM could actually be amyloidogenic. The final category, non-PCD, is a heterogeneous group that includes cDNA derived sequences from polyclonal healthy bone marrow, disease-related LCs and sequences of solved LC structures from the Protein Data Bank (www.rcsb.org/pdb).…”
Section: Discussionmentioning
confidence: 99%
“…This set is composed of LCs from other PCDs, not only from MM ( n = 152) but also from LCDD ( n = 7) and WM ( n = 4). Although LCDD sequences by definition do not form fibrils [25], it is possible that some of the MM sequences could be amyloidogenic, as up to 10–20% of MM cases can develop fibrillar LC deposits [2628]; thus, it is possible that some of the sequences classified as MM could actually be amyloidogenic. The final category, non-PCD, is a heterogeneous group that includes cDNA derived sequences from polyclonal healthy bone marrow, disease-related LCs and sequences of solved LC structures from the Protein Data Bank (www.rcsb.org/pdb).…”
Section: Discussionmentioning
confidence: 99%
“…Ig deposits are frequently associated with B cell malignancy (16). Autoantigens may be involved in the stimulation of B cell proliferative diseases, as suggested by the restricted use of particular V genes (17) and the accumulation of somatic mutations (18). Autoantigens may also participate in the formation of Ig deposits, such as in mixed cryoglobulinemia where precipitates reflect Ab-Ag interactions (19).…”
mentioning
confidence: 99%
“…To this end, we combined biochemical, spectroscopic, and bioinformatics methods with hydrogen-deuterium exchange (HDX) mass spectrometry (MS) to explore 14 patient-derived and engineered LCs and their domain fragments from two closely related κ1 sub-families. Patient-derived proteins were associated with either AL amyloidosis or multiple myeloma (MM), another monoclonal Ig disease wherein most patients do not develop AL [26]. In our study, MM LC was used as a naturally occurring non-AL control.…”
Section: Introductionmentioning
confidence: 99%