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 co nsidered as useful clonal markers in lymphoproliferative disorders of B- an d T-cell lineage, and are frequently used for the detection of minimal resi dual disease (MRD). In this paper, we report on the unexpected results of a n extensive analysis of TCR-F chain gene rearrangement frequencies and patt erns 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, t he overall incidence of non-deleted TCR-delta gene rearrangements in ALL wa s 47% (206/438), 52% in initial ALL (58/112) and 45% in relapsed ALL (148/3 26). As expected, the majority of B-cell precursor (BCP) ALL had incomplete V delta2-D delta3 or D delta2-D delta3 TCR-delta gene rearrangements, wher eas most T-ALL showed complete rearrangements of the TCR-delta gene locus ( V delta1-J delta1, V delta2-J delta1, V delta3-J delta1). However. unexpect edly, 5/206 rear ranged TCR-delta alleles in BCP-ALL showed a complete V de lta- (D delta)-J delta gene rearrangement pattern, and 3/31 T-ALL had an in complete recombination. Theoretically, complete TCR-delta gene rearrangemen ts should not occur in cells other than T-lymphocytes and have only been re ported once previously in BCP-ALL. The data contribute to the discussion ab out the reliable screening for clonal markers in ALL.