MULTICLONALITY AND ALTERED RFLP PATTERNS FOR IMMUNOGLOBULIN HEAVY-CHAIN AND T-CELL RECEPTOR GENES IN RELAPSING LYMPHOMAS

Background: Alteration of morphological appearance as well as of clini cal behaviour is common in relapsing non-Hodgkin's lymphomas. The aim of this study was to investigate the stability of the genes encoding t he immunoglobulin heavy-chain and the T-cell receptor during the cours e of the disease in relapsing non-Hodgkin's lymphomas. Material and me thods: Nineteen patients with relapsed or progressive non-Hodgkin's ly mphomas were analysed with respect to alterations of the restriction f ragment length polymorphism (RFLP) pattern for Ig heavy chain (IgH) us ing probes for the Cmu and J regions and for T-cell receptor (T-beta, T-gamma chain) genes. DNA was extracted from tumour material taken at different occasions during the course of the disease. Results: All 19 cases showed clonal rearrangements of the IgH locus, and 2 cases showe d simultaneous rearrangement of the genes coding for the T-cell recept ors. Three or more rearranged bands, indicating more than one malignan t clone, were detected in 1 case at the time of the diagnosis and in 5 /19 (26%) cases in DNA from samples taken at relapse, all 6 cases show ing discordant or transformed morphology. Altogether, in 11 out of 19 cases (58%), changes of the IgH rearrangement pattern could be visuali zed by RFLP. In all these cases except one, the new RFLP pattern inclu ded at least one rearranged band from the pattern of the first taken s ample. In one case a clonal T-gamma receptor gene rearrangement was de tected in a diagnostic sample but not in a sample taken at relapse. In 4 out of 6 cases with transformed lymphomas, clonal changes were obse rved at time of transformation. Evolution of clones with different RFL P patterns in different compartments were observed in 1 out of 6 studi ed cases. Conclusions: The present study illustrates that non-Hodgkin' s lymphomas are unstable in their IgH genome. The observations of clon al evolution, multiclonality, and different clones in different compar tments offer an explanation to the troublesome situation when treating relapsed lymphomas.