T-cell prolymphocytic leukaemia: antigen receptor gene rearrangement and anovel mode of MTCP1 B1 activation

T-cell prolymphocytic leukaemia (T-PLL) is a sporadic, mature T-cell disord er in which there is usually an aberrant T-cell receptor alpha (TCRA) rearr angement that activates the TCL1 or MTCP1-B1 oncogenes. As mutations of the Ataxia Telangiectasia (A-T) gene, ATM, are frequent in T-PLL and as ATM se ems to act as a tumour suppressor through a mechanism involving V(D)J recom bination, we examined V(D)J recombination in T-PLL. Using Southern blotting and the polymerase chain reaction, two of 60 TCRG coding joints were abnor mal. In all cases, both TCRD alleles were deleted, IGH was germline, and pa tterns of TCRB and TCRA rearrangement were normal. However, in a case harbo uring t(X;7)(q28;q35), we identified TCRB segment J beta 2.7 juxtaposed to MTCP1 exon 1. This is the first time that TCRB has been implicated in MTCP1 B1 activation. The structure of the breakpoint supports a model in which t ranslocation activates a cryptic MTCP1 promoter. This analysis of V(D)J rec ombination is consistent with it being a variable that is independent of AT M in T-PLL.