Novel T-cell receptor delta gene rearrangement involving a recombining element located 2.6 kb 3 ' from the V delta 2 gene segment

In this study, we describe a novel T-cell receptor delta (TCR delta) gene r earrangement observed in acute myeloid leukemia with coexpression of T-lymp hoid antigens (Ly + AML) and in peripheral blood leukocytes (PBL) from one out of ten healthy donors. The rearrangement was identified by Southern blo t analysis using a joining region (J delta1) specific probe and amplified b y polymerase chain reaction (PCR) with a variable region (V delta2) and J d elta1 specific primers. The nucleotide sequence analysis of an atypical 300 0 bp PCR product allowed localization of the breakpoint within the TCR delt a gene locus, 2.6 kb 3' from the V delta2 gene segment. A regular D delta2- D delta3-J delta1 joining was found at the 3' end of the breakpoint, indica ting that the rearrangement was mediated by the VDJ recombinase, but no TCR delta gene segment was detected at the 5' end. Analysis of the germline se quence 3' from the breakpoint revealed an isolated recombination signal seq uence (RSS) capable of initiating a rearrangement. The RSS motif described by us is the second TCR delta recombining element (delta Rec2). The delta R ec2(D delta )J delta1 recombination is a rather rare event and can be found in acute leukemia and in PBL from healthy individuals. Most likely, the no nfunctional delta Rec2(D delta )J delta1 rearrangement is a transient step during the VDJ recombination. It may potentially lead to deletion of the de lta Rec2(D delta )J delta1 complex and either to direct joining of a V delt a region to one of the downstream J delta regions or to a rearrangement of the TCR alpha gene. (C) 2001 Published by Elsevier Science Ltd.