Rearrangement of T-cell Receptor (Delta, Gamma and Beta) Genes and its Significance in T-cell Chronic Leukaemias.

Abstract

The configuration of the delta, gamma and beta TCR genes and IgH genes was studied using appropriate DNA probes in 12 patients previously diagnosed as having T-cell chronic leukaemia. One or more TCR genes showed rearrangement and/or deletion in 11 patients, whereas rearrangement of IgH genes were seen in 3 patients only. TCR genes showed four distinct patterns: (a) rearrangement and/or deletion of each of the three TCR genes (7 patients), (b) re-arrangement of two TCR genes (3 patients), (c) rearrangement/deletion of one TCR gene only (1 patient), (d) germ-line state of all TCR genes (1 patient). These patterns had no demonstrable relationship with the clinical status either at the time of diagnosis or during the subsequent course of the disease. The findings provided unequivocal evidence of T-cell lineage of the leukaemic cells in 10 out of 12 patients. In one patient the lineage of leukaemic cells remained indeterminate. In the last patient the germ-line state of all TCR genes and rearrangement of both IgH alleles genes indicated that the leukaemia was of B-cell origin, even though the leukaemic cells had other features regarded as characteristic of T-lymphocytes. The different patterns of TCR genes, seen in the context of the hierarchical nature of the rearrangement process, suggest that the leukaemic transformation occurred at different stages of T-cell ontogeny and was followed by arrest of subsequent TCR gene rearrangement.