Ferrero, Simone, Capello, Daniela, Svaldi, Mirija, Boi, Michela, Gatti, Daniela, Drandi, Daniela, Rossi, Davide, Barbiero, Sara, Mantoan, Barbara, Mantella, Elisabetta, Zanni, Manuela, Ghione, Paola, Larocca, Alessandra, Passera, Roberto, Bertoni, Francesco, Gattei, Valter, Forconi, Francesco, Laurenti, Luca, Del Poeta, Giovanni, Marasca, Roberto, Cortelazzo, Sergio, Gaidano, Gianluca, Palumbo, Antonio, Boccadoro, Mario and Ladetto, Marco (2012) Multiple myeloma shows no intra-disease clustering of immunoglobulin heavy chain genes. Haematologica, 97 (6), 849-853. (doi:10.3324/haematol.2011.052852). (PMID:22207685)
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.
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