Unusual T-cell receptor-delta gene rearrangement patterns revealed by screening of a large series of childhood acute lymphoblastic leukaemia by multiplex polymerase chain reaction.

Rearrangements of the T-cell receptor (TCR) and immunoglobulin genes are considered as useful clonal markers in lymphoproliferative disorders of B- and T-cell lineage, and are frequently used for the detection of minimal residual disease (MRD). In this paper, we report on the unexpected results of an extensive analysis of TCR-delta chain gene rearrangement frequencies and patterns in leukaemic bone marrow DNA samples collected from 438 children with initial (n = 112) or relapsed (n = 326) acute lymphoblastic leukaemia (ALL). By applying a previously described multiplex polymerase chain reaction, the overall incidence of non-deleted TCR-delta gene rearrangements in ALL was 47% (206/438), 52% in initial ALL (58/112) and 45% in relapsed ALL (148/326). As expected, the majority of B-cell precursor (BCP) ALL had incomplete Vdelta2-Ddelta3 or Ddelta2-Ddelta3 TCR-delta gene rearrangements, whereas most T-ALL showed complete rearrangements of the TCR-delta gene locus (Vdelta1-Jdelta1, Vdelta2-Jdelta1, Vdelta3-Jdelta1). However, unexpectedly, 5/206 rearranged TCR-delta alleles in BCP-ALL showed a complete Vdelta-(Ddelta)-Jdelta gene rearrangement pattern, and 3/31 T-ALL had an incomplete recombination. Theoretically, complete TCR-delta gene rearrangements should not occur in cells other than T-lymphocytes and have only been reported once previously in BCP-ALL. The data contribute to the discussion about the reliable screening for clonal markers in ALL.