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

Background. Characterization of the immunoglobulin genes repertoire improved the 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 receptors clusters. Results. Compared to the normal immunoglobulin repertoire, multiple myeloma displayed only modest differences involving few genes, demonstrating that 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 aminoacids. 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.