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Analysis of V(lambda)-J(lambda) expression in plasma cells from primary (AL) amyloidosis and normal bone marrow identifies 3r (lambdaIII) as a new amyloid-associated germline gene segment.
Blood. 2002 Aug 01; 100(3):948-53.Blood

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 lambda isotype and lambdaVI family light-chain proteins. To provide insights into these issues, we obtained complete nucleotide sequences of monoclonal V(lambda) 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 lambdaIII 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 lambdaIII and lambdaVI families, namely 3r (22% of cases, lambdaIII) and 6a (20%, lambdaVI), contributed equally to encode 42% of amyloid V(lambda) 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, chi2 test); (5) the J(lambda)2/3 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 J(lambda)2/3 rearrangement in amyloid (11 of 12 cases) versus polyclonal 3r light chains (13 of 22 cases). These findings demonstrate that V(lambda)-J(lambda) 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 lambda light-chain overrepresentation typical of this disorder.

Authors+Show Affiliations

Internal Medicine and Medical Oncology, Department of Internal Medicine, University of Pavia, IRCCS Policlinico S. Matteo, Pavia, Italy.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

12130507

Citation

Perfetti, Vittorio, et al. "Analysis of V(lambda)-J(lambda) Expression in Plasma Cells From Primary (AL) Amyloidosis and Normal Bone Marrow Identifies 3r (lambdaIII) as a New Amyloid-associated Germline Gene Segment." Blood, vol. 100, no. 3, 2002, pp. 948-53.
Perfetti V, Casarini S, Palladini G, et al. Analysis of V(lambda)-J(lambda) expression in plasma cells from primary (AL) amyloidosis and normal bone marrow identifies 3r (lambdaIII) as a new amyloid-associated germline gene segment. Blood. 2002;100(3):948-53.
Perfetti, V., Casarini, S., Palladini, G., Vignarelli, M. C., Klersy, C., Diegoli, M., Ascari, E., & Merlini, G. (2002). Analysis of V(lambda)-J(lambda) expression in plasma cells from primary (AL) amyloidosis and normal bone marrow identifies 3r (lambdaIII) as a new amyloid-associated germline gene segment. Blood, 100(3), 948-53.
Perfetti V, et al. Analysis of V(lambda)-J(lambda) Expression in Plasma Cells From Primary (AL) Amyloidosis and Normal Bone Marrow Identifies 3r (lambdaIII) as a New Amyloid-associated Germline Gene Segment. Blood. 2002 Aug 1;100(3):948-53. PubMed PMID: 12130507.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Analysis of V(lambda)-J(lambda) expression in plasma cells from primary (AL) amyloidosis and normal bone marrow identifies 3r (lambdaIII) as a new amyloid-associated germline gene segment. AU - Perfetti,Vittorio, AU - Casarini,Simona, AU - Palladini,Giovanni, AU - Vignarelli,Maurizio Colli, AU - Klersy,Catherine, AU - Diegoli,Marta, AU - Ascari,Edoardo, AU - Merlini,Giampaolo, PY - 2002/7/20/pubmed PY - 2002/9/7/medline PY - 2002/7/20/entrez SP - 948 EP - 53 JF - Blood JO - Blood VL - 100 IS - 3 N2 - 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 lambda isotype and lambdaVI family light-chain proteins. To provide insights into these issues, we obtained complete nucleotide sequences of monoclonal V(lambda) 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 lambdaIII 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 lambdaIII and lambdaVI families, namely 3r (22% of cases, lambdaIII) and 6a (20%, lambdaVI), contributed equally to encode 42% of amyloid V(lambda) 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, chi2 test); (5) the J(lambda)2/3 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 J(lambda)2/3 rearrangement in amyloid (11 of 12 cases) versus polyclonal 3r light chains (13 of 22 cases). These findings demonstrate that V(lambda)-J(lambda) 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 lambda light-chain overrepresentation typical of this disorder. SN - 0006-4971 UR - https://www.unboundmedicine.com/medline/citation/12130507/Analysis_of_V_lambda__J_lambda__expression_in_plasma_cells_from_primary__AL__amyloidosis_and_normal_bone_marrow_identifies_3r__lambdaIII__as_a_new_amyloid_associated_germline_gene_segment_ L2 - https://ashpublications.org/blood/article-lookup/doi/10.1182/blood-2002-01-0114 DB - PRIME DP - Unbound Medicine ER -