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Multiple myeloma shows no intra-disease clustering of immunoglobulin heavy chain genes

Authors :
Daniela Capello
Mario Boccadoro
Valter Gattei
Barbara Mantoan
Manuela Zanni
Giovanni Del Poeta
Alessandra Larocca
Roberto Passera
Roberto Marasca
Luca Laurenti
Davide Rossi
Simone Ferrero
Paola Ghione
Francesco Bertoni
Gianluca Gaidano
Sergio Cortelazzo
Daniela Drandi
Antonio Palumbo
Elisabetta Mantella
Francesco Forconi
Sara Barbiero
Michela Boi
Mirija Svaldi
Marco Ladetto
Daniela Gatti
Publication Year :
2012

Abstract

Background Characterization of the immunoglobulin gene repertoire has improved our understanding of the immunopathogenesis of lymphoid tumors. Early B-lymphocyte precursors of multiple myeloma are known to exist and might be susceptible to antigenic drive. Design and Methods To verify this hypothesis, we collected a database of 345 fully readable multiple myeloma immunoglobulin sequences. We characterized the immunoglobulin repertoire, analyzed the somatic hypermutation load, and investigated for stereotyped receptor clusters. Results Compared to the normal immunoglobulin repertoire, multiple myeloma displayed only modest differences involving only a few genes, showing that the myeloma immunoglobulin repertoire is the least skewed among mature B-cell tumors. Median somatic hypermutation load was 7.8%; median length of complementarity determining-region 3 was 15.5 amino acids. Clustering analysis showed the absence of myeloma specific clusters and no similarity with published chronic lymphocytic leukemia or lymphoma subsets. Conclusions Analysis of multiple myeloma immunoglobulin repertoire does not support a pathogenetic role for antigen selection in this tumor.

Details

Language :
English
Database :
OpenAIRE
Accession number :
edsair.doi.dedup.....4d73ff6c60a348972091b3b4d3800ef8