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• W1594036575 abstract "Abstract Primary (AL) amyloidosis is a plasma cell dyscrasia characterized by extracellular deposition of monoclonal light-chain variable region (V) fragments in the form of amyloid fibrils. Light-chain amyloid is rare, and it is not fully understood why it occurs in only a fraction of patients with a circulating monoclonal component and why it typically associates with λ isotype and λVI family light-chain proteins. To provide insights into these issues, we obtained complete nucleotide sequences of monoclonal Vλ regions from 55 consecutive unselected cases of primary amyloidosis and the results were compared with the light-chain expression profile of polyclonal marrow plasma cells from 3 healthy donors (a total of 264 sequences). We demonstrated that: (1) the λIII family is the most frequently used both in amyloidosis (47%) and in polyclonality (43%); (2) both conditions are characterized by gene restriction; (3) a very skewed repertoire is a feature of amyloidosis, because just 2 germline genes belonging to the λIII and λVI families, namely 3r (22% of cases, λIII) and 6a (20%, λVI), contributed equally to encode 42% of amyloid Vλ regions; (4) these same 2 gene segments have a strong association with amyloidosis if their prevalences are compared with those in polyclonal conditions (3r, 8.3%,P = .024; 6a, 2.3%, P = .0008, χ2 test); (5) the Jλ2/3 segment, encoding the fourth framework region, appears to be slightly overrepresented in AL (83% versus 67%, P = .03), and this might be related to preferential Jλ2/3 rearrangement in amyloid (11 of 12 cases) versus polyclonal 3r light chains (13 of 22 cases). These findings demonstrate that Vλ-Jλ expression is more restricted in plasma cells from amyloidosis than from polyclonal bone marrow and identify 3r as a new disease-associated gene segment. Overusage of just 2 gene segments,3r and 6a, can thus account for the λ light-chain overrepresentation typical of this disorder." @default.
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• W1594036575 date "2002-08-01" @default.
• W1594036575 modified "2023-10-16" @default.
• W1594036575 title "Analysis of Vλ-Jλ expression in plasma cells from primary (AL) amyloidosis and normal bone marrow identifies 3r(λIII) as a new amyloid-associated germline gene segment" @default.
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• W1594036575 doi "https://doi.org/10.1182/blood-2002-01-0114" @default.
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