T cell receptor δ gene rearrangements in acute lymphoblastic leukemia

Abstract

Using a newly isolated cDNA clone encoding the TCR-δ gene and genomic probes, we have analyzed T cell receptor (TCR) δ gene rearrangement in 19 patients with T cell acute lymphoblastic leukemia (T-ALL) and 29 patients with B-precursor ALL. Five out of seven CD3- T-ALL and 4 of 12 CD3+ T-ALL showed bi-allelic rearrangements of the TCR-δ gene. In three CD3+ patients, a single allelic TCR-δ gene rearrangement was observed with rearrangement of the TCR-α gene on the other allele. In five CD3+ patients with bi-allelic rearrangements of the TCR-α gene, the TCR-δ gene locus was deleted. Transcription of the TCR-δ gene was also analyzed in six T-ALL. Five patients expressed TCR-δ transcripts. Only one T-ALL, presumably derived from the most immature T lineage cells, did not have TCR-δ transcripts, but expressed TCR-γ and 1.0-kb truncated TCR-β transcripts. In B-precursor ALL, 20 patients (69%) showed rearrangements of the TCR-δ gene. The frequency of TCR-δ gene rearrangement was higher than TCR-α (59%), γ (52%), or β (31%) genes. These findings suggest that TCR-α gene rearrangements may take place after rearrangements of the TCR-δ gene with concomitant deletion of rearranged TCR-δ genes in T cell differentiation. Among leukemic cells of B lineage, the TCR-δ gene is the earliest rearranging TCR gene, followed by TCR-γ and β gene rearrangements.