Novel T-cell receptor delta gene rearrangement involving a recombining element located 2.6 kb 3' from the Vdelta2 gene segment.

In this study, we describe a novel T-cell receptor delta (TCRdelta) gene rearrangement observed in acute myeloid leukemia with coexpression of T-lymphoid antigens (Ly+AML) and in peripheral blood leukocytes (PBL) from one out of ten healthy donors. The rearrangement was identified by Southern blot analysis using a joining region (Jdelta1) specific probe and amplified by polymerase chain reaction (PCR) with a variable region (Vdelta2) and Jdelta1 specific primers. The nucleotide sequence analysis of an atypical 3000 bp PCR product allowed localization of the breakpoint within the TCRdelta gene locus, 2.6 kb 3' from the Vdelta2 gene segment. A regular Ddelta2-Ddelta3-Jdelta1 joining was found at the 3' end of the breakpoint, indicating that the rearrangement was mediated by the VDJ recombinase, but no TCRdelta gene segment was detected at the 5' end. Analysis of the germline sequence 3' from the breakpoint revealed an isolated recombination signal sequence (RSS) capable of initiating a rearrangement. The RSS motif described by us is the second TCRdelta recombining element (deltaRec2). The deltaRec2(Ddelta)Jdelta1 recombination is a rather rare event and can be found in acute leukemia and in PBL from healthy individuals. Most likely, the nonfunctional deltaRec2(Ddelta)Jdelta1 rearrangement is a transient step during the VDJ recombination. It may potentially lead to deletion of the deltaRec2(Ddelta)Jdelta1 complex and either to direct joining of a Vdelta region to one of the downstream Jdelta regions or to a rearrangement of the TCRalpha gene.