Immunoglobulin V H gene replacements in a T-cell lymphoblastic lymphoma

Abstract

We have analysed the rearrangement status of the immunoglobulin heavy (IgH) chain locus during progression of a T-cell lymphoblastic lymphoma displaying multiple IgH rearrangements as demonstrated by variable heavy (V h ) gene family specific polymerase chain reaction (PCR) analysis. The tumor was found to undergo diversification at the IgH locus between diagnosis and relapse through a mechanism of V h to V h DJ h replacement. In subsets of the tumor at relapse, two separate V h gene segments were found to have replaced the V h gene utilized by a V h DJ h rearrangement identified at diagnosis. The observed V h gene replacement events appear to have been mediated by a heptamer sequence homologous to the heptamer of the recombination signal sequence (RSS) located internally in the V h gene segment. These results support the notion that V h replacements contribute to the diversification of immunoglobulin genes.