Molecular analysis of T-cell receptor transcripts in a human T-cell leukemia bearing a t(1;14) and an inv(7); cell surface expression of a TCR-β chain in the absence of α chain

The polymerase chain reaction (PCR) was used to amplify cDNA in order to characterize normal and hybrid T-cell receptor (TCR) gene rearrangements derived from a T-cell acute lymphoblastic leukemia (T-ALL) bearing a chromosome 7 inversion. The nucleotide sequence analysis of the amplified product showed the presence of an out-of-frame Vβ/Jγ/Cγ transcript and an in-frame Vγ/Jγ/Cβ transcript which result from an interlocus recombination between the TCR-β and γ loci and the transcription of the reciprocal hybrid TCR gene. The sequence analysis of the reciprocal DNA segment directly involved in the breakpoint of the inversion showed a recombination between a Jγ-sequence heptamer signal and a coding Jβ gene segment. The exonuclease nibbling of each DNA extremity and the non-templated nucleotide insertion observed at both coding and reciprocal joints demonstrate that the inversion is mediated by the lymphocyte recombinase complex. During T-cell differentiation, TCR-β genes are rearranged prior to TCR-α genes. In the present case of T-ALL, we have shown that TCR-δ genes are rearranged at both loci, excluding productive rearrangements of TCR-α genes. The molecular analysis of the normal TCR genes derived from the leukemic cells revealed the presence of productively rearranged TCR-β, γ, and δ genes. Cell surface staining of these cells showed the presence of CD3 molecules and of a TCR-β chain corresponding to the normal β allele expressed in a disulf ide-linked complex with a protein which is not TCR-α, γ, or δ. This could represent the cell surface expression of the hybrid TCR-Vγ/Cβ protein or the expression of a TCR-β homodimer.