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

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

Research output: Contribution to journalArticle

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.

Original languageEnglish
Pages (from-to)849-853
Number of pages5
JournalHaematologica
Volume97
Issue number6
DOIs
Publication statusPublished - Jun 1 2012

Keywords

  • Antigen selection
  • Heavy chain gene
  • Immunoglobulin
  • Multiple myeloma

ASJC Scopus subject areas

  • Hematology

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    Ferrero, S., Capello, D., Svaldi, M., Boi, M., Gatti, D., Drandi, D., Rossi, D., Barbiero, S., Mantoan, B., Mantella, E., Zanni, M., Ghione, P., Larocca, A., Passera, R., Bertoni, F., Gattei, V., Forconi, F., Laurenti, L., del Poeta, G., ... Ladetto, M. (2012). Multiple myeloma shows no intra-disease clustering of immunoglobulin heavy chain genes. Haematologica, 97(6), 849-853. https://doi.org/10.3324/haematol.2011.052852