ALTERATIONS OF THE IMMUNOGLOBULIN HEAVY-CHAIN LOCUS IN PROGRESSIVE B-CELL LYMPHOMAS

Twenty-two patients with relapsed or progressive B-cell lymphomas (BCL ) were analysed for alterations in the rearrangement status in the imm unoglobulin heavy (IgH) chain gene in samples obtained on different oc casions during the course of the disease. The analysis was performed u sing Southern blot hybridization of the ISH gene and polymerase chain reaction (PCR) amplification of the V-H gene families combined with si ngle-strand conformation polymorphism (SSCP) analysis. Using Southern blot analysis, we found that all 22 lymphomas displayed clonal IgH rea rrangements, and changes during tumour progression occurred in 8 cases . These alterations were mainly observed in cases with follicular or t ransformed lymphomas. More than one malignant (sub)clone, indicated by more than two rearranged bands, was detected in one case at diagnosis and in three cases at relapse. Outgrowth of subclones with divergent rearrangement patterns in different compartments was also observed in 2 out of 8 cases. PCR-SSCP analysis indicated that all 15 cases studie d displayed clonal rearrangements and in 6 cases altered rearrangement patterns were detected in later samples. Southern blotting and PCR-SC CP analysis gave equivalent results. No association was found between time to relapse or survival time and alterations in rearrangement patt ern. The present study illustrates that the neoplastic cell clones in BCL often display alterations in their IgH locust but the significance of this feature remains to be clarified.