@article{3053968,
    title = "Origin and diversification of the clonogenic cell in multiple myeloma:
lessons from the immunoglobulin repertoire",
    author = "Kosmas, C and Stamatopoulos, K and Stavroyianni, N and Zoi, K and and Belessi, C and Viniou, N and Kollia, P and Yataganas, X",
    journal = "Leukemia Research",
    year = "2000",
    volume = "14",
    number = "10",
    pages = "1718-1726",
    publisher = "Nature Publishing Group",
    issn = "0145-2126",
    doi = "10.1038/sj.leu.2401908",
    keywords = "immunoglobulin genes; somatic hypermutation; multiple myeloma",
    abstract = "The study of immunoglobulin genes in multiple myeloma over the last
decade has provided important information regarding biology, ontogenetic
assignment, disease evolution, pathogenic consequences and
tumor-specific therapeutic intervention. Detailed analysis of V-H genes
has revealed the clonal relationship between switch variants expressed
by the bone marrow plasma cell and myeloma progenitors in the marrow and
peripheral blood. Regarding V-H usage, a bias was found against the
V4-34 gene encoding antibodies with cold agglutinin specificity
(anti-I/i), thus explaining in part the absence of autoimmune phenomena
in myeloma compared to other B cell lymphoproliferative disorders.
However, in some studies a substantial number of cases analyzed were
carrying the rearranged Hum kappa v325 V kappa gene, known to be over
utilized by B cell chronic lymphocytic leukemia clones and possessing
autoantibody binding activity. V-H genes accumulate somatic
hypermutations following a distribution compatible with antigen
selection, but with no intraclonal heterogeneity. The analysis of V
kappa genes indicates a bias in usage of V kappa I family members;
somatic hypermutation, in line with antigen selection, of the expressed
V kappa genes is higher than any other B cell lymphoid disorder. Similar
conclusions were reached far V lambda genes; in this case, the analysis
raises the controversial issue of N nucleotide insertion at V lambda-J
lambda junctions, apparently as a result of TdT activity. A
complementary imprint of antigen selection as evidenced by somatic
hypermutation of either the V-H or V-L clonogenic genes has been
observed. The absence of ongoing somatic mutations in either V-H or V-L
genes gives rise to the notion that the cell of origin in myeloma is a
post-germinal center memory B cell."
}