John Libbey Eurotext



Tranlocations involving the immunoglobulin heavy chain gene in multiple myeloma: a universal phenomenon? Volume 6, issue 4, Juillet - Août 2000


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Laboratoire d’hématologie et Inserm U. 463, centre hospitalier universitaire, 9, quai Moncouso, 44093, Nantes cedex 1. 2 Inserm U. 463, Nantes.

Cytogenetic analysis is a difficult challenge in multiple myeloma (MM), especially because of the low proliferative index observed in malignant plasma cells. Consequently, very few recurrent cytogenetic abnormalities have been reported in MM. Recently, the use of molecular technologies such as Southern blot or fluorescence in situ hybridization enabled to circumvent this problem, and demonstrated that virtually all human myeloma cell lines and about 60 % of patients with MM displayed illegitimate rearrangement involving the IGH gene (encoding the immunoglobulin heavy chain) at 14q32. In cell lines, four recurrent partner genes have been identified: FGFR3 at 4p16, CCND1 at 11q13, MAF at 16q23, and MYC at 8q24, each involved in 20 % to 25 % of the cell lines. In contrast, in patients, only two of these genes are recurrently involved : CCND1 in 16 % of cases, and FGFR3 in 12 %. In the other patients, multiple partner chromosomal regions are observed. Moreover, these illegitimate IGH rearrangements are probably early events. We have shown that they were observed in at least 50 % of individuals with monoclonal gammopathy of undetermined significance, a non-malignant condition characterized by the expansion of a clonal plasma cell population. Thus, all these data highlight the deregulation of the IGH gene in the first steps of plasma cell oncogenesis.