Molecular analysis of immunoglobulin genes in multiple myeloma

Citation
C. Kosmas et al., Molecular analysis of immunoglobulin genes in multiple myeloma, LEUK LYMPH, 33(3-4), 1999, pp. 253-265
Citations number
71
Categorie Soggetti
Hematology,"Onconogenesis & Cancer Research
Journal title
LEUKEMIA & LYMPHOMA
ISSN journal
10428194 → ACNP
Volume
33
Issue
3-4
Year of publication
1999
Pages
253 - 265
Database
ISI
SICI code
1042-8194(199904)33:3-4<253:MAOIGI>2.0.ZU;2-J
Abstract
The study of immunoglobulin genes in multiple myeloma over the last five ye ars has provided important information regarding biology, ontogenetic locat ion, disease evolution, pathogenic consequences and tumor-specific therapeu tic intervention with idiotypic vaccination, Detailed analysis of V-H genes has revealed clonal relationship between switch variants expressed by the bone marrow plasma cell and myeloma progenitors in the marrow and periphera l blood. V-H gene usage is biased against V4-34 (encoding antibodies with c old agglutinin specificity; anti-l/i) explaining the absence of autoimmune phenomena in myeloma compared to other B-cell lymphoproliferative disorders . V-H genes accumulate somatic hypermutations following a distribution comp atible with antigen selection, but with no intraclonal heterogeneity. V-L g enes indicate a bias in usage of V kappa I family members and somatic hyper mutation, in line with antigen selection, of the expressed V kappa genes i s higher than any other B-cell lymphoid disorder. A complementary imprint o f 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. Clinical app lication of sensitive PCR methods in order to detect clonal immunoglobulin gene rearrangements has made relevant the monitoring and follow-up of minim al residual disease in stem cell autografts and after myeloablative therapy . The fact that surface immunoglobulin V-H and V-L sequences consitute uniq ue tumor-specific antigenic determinants has stimulated investigators to de vise strategies aiming to generate active specific immunity against the idi otype of malignant B-cells in myeloma by constructing vaccines based on exp ressed single-chain Fv fragments, DNA plasmids carrying V-H+V-L clonogenic genes for naked DNA vaccination, or dendritic cell-based vaccination armed with the tumor-specific idiotype.