A mechanism for cross-lineage gene rearrangements in B-cell neoplasm.

Abstract

The organization of immunoglobulin heavy chain (IgH) gene of B precursor cell acute lymphoblastic leukemia (ALL) was examined in order to elucidate the mechanism causing simultaneous TCR gene rearrangements. Study using a 5'D probe lying 20 kb upstream of IgH D region genes was useful to distinguish diversity(D)-joining(J) recombination(DJ) from variable(V)-DJ recombination(VDJ). Indeed, IgH gene structures determined by 5'D study well correlated to those recognized by DJ or VDJ transcripts. IgH gene rearrangements of B precursor cell ALL showed developmentally restricted gene recombination; DJ/DJ genotype in the most immature stage and VDJ/VDJ genotype in the relatively mature stage. B precursor cell ALL with simultaneous rearrangements were frequently found in relatively mature cells, i.e., CD20 expressing cells on their surface. Furthermore, most of such dual genotypic ALL showed that at least one allele of IgH genes was VDJ recombination. This finding suggests that dual genotype was the incidental product by a putative common recombinase during the process of VH gene rearrangements. Moreover, since IgH gene rearrangements of acute unclassified leukemia with dual genotype were DQ52 genotype, which indicates abortive gene rearrangements, it was also thought that dual genotype occurred due to the pluripotentiality of the stem cell.