Identification of clonal immunoglobulin λ light-chain gene rearrangements in AL amyloidosis using next-generation sequencing.
Exp Hematol
; 101-102: 34-41.e4, 2021 09.
Article
in En
| MEDLINE
| ID: mdl-34411686
ABSTRACT
Amyloid light-chain (AL) amyloidosis is caused by deposition of abnormally folded clonal immunoglobulin (Ig) light chains made by malignant plasma cells in the bone marrow (BM), leading to multiorgan dysfunction. However, little is known of the factors that regulate the organ tropism of amyloid deposition in this disease. We aimed to identify the clonal composition of Igλ light-chain variable region (IGLV) genes in BM cells in patients with AL amyloidosis using next-generation sequencing. Based on our definition of the clonal IGLV rearrangement (dominant clone >2.5%, dominant cluster >5%), we identified clonal IGLV in 33 of 38 patients with AL amyloidosis (86.8%), 6 of 9 with monoclonal gammopathy of undetermined significance (67%), and 7 of 7 with multiple myeloma (100%). The clones in AL amyloidosis were significantly smaller than those in multiple myeloma (p < 0.01) but comparable to those in monoclonal gammopathy of undetermined significance. Importantly, in patients with AL amyloidosis, the difference in involved and uninvolved free light chains was not correlated with the clonal size of BM plasma cells in our repertoire analysis using NGS. In summary, the clonal composition of IGLV genes in the BM was successfully identified in most patients with AL amyloidosis using NGS. The clonal size of plasma cells in the BM is small, and small malignant clones of plasma cells may secrete free light chi and cause light chain depositions in AL amyloidosis.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Gene Rearrangement
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Immunoglobulin lambda-Chains
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Immunoglobulin Light-chain Amyloidosis
Type of study:
Diagnostic_studies
/
Prognostic_studies
Limits:
Adult
/
Aged
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Aged80
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Female
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Humans
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Male
/
Middle aged
Language:
En
Journal:
Exp Hematol
Year:
2021
Document type:
Article
Affiliation country: