Novel T-cell receptor δ gene rearrangement involving a recombining element located 2.6 kb 3′ from the Vδ2 gene segment

Abstract 

In this study, we describe a novel T-cell receptor δ (TCRδ) 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 (Jδ1) specific probe and amplified by polymerase chain reaction (PCR) with a variable region (Vδ2) and Jδ1 specific primers. The nucleotide sequence analysis of an atypical 3000 bp PCR product allowed localization of the breakpoint within the TCRδ gene locus, 2.6 kb 3′ from the Vδ2 gene segment. A regular Dδ2–Dδ3–Jδ1 joining was found at the 3′ end of the breakpoint, indicating that the rearrangement was mediated by the VDJ recombinase, but no TCRδ 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 TCRδ recombining element (δRec2). The δRec2(Dδ)Jδ1 recombination is a rather rare event and can be found in acute leukemia and in PBL from healthy individuals. Most likely, the nonfunctional δRec2(Dδ)Jδ1 rearrangement is a transient step during the VDJ recombination. It may potentially lead to deletion of the δRec2(Dδ)Jδ1 complex and either to direct joining of a Vδ region to one of the downstream Jδ regions or to a rearrangement of the TCRα gene.

Keywords:  Acute myeloid leukemia with coexpression of T-lymphoid antigens, Rearrangement, T-Cell receptor δ, δRec2