Molecular Involvement of the pvt-1 Locus in a γ/δ T-Cell Leukemia Bearing a Variant t(8;14)(q24;q11) Translocation

A highly malignant human T-cell receptor (TCR) γ/δ⁺ T-cell leukemia was shown to have a productive rearrangement of the TCR δ locus on one chromosome 14 and a novel t(8;14)(q24;q11) rearrangement involving the Jδ1 gene segment on the other chromosome 14. Chromosome walking coupled with pulsed-field gel electrophoretic (PFGE) analysis determined that the TCR Jδ1 gene fragment of the involved chromosome was relocated approximately 280 kb downstream of the c-myc proto-oncogene locus found on chromosome band 8q24. This rearrangement was reminiscent of the Burkitt's lymphoma variants that translocate to a region identified as the pvt-1 locus. Sequence comparison of the breakpoint junctions of interchromosomal rearrangements in T-cell leukemias involving the TCR δ-chain locus revealed novel signal-like sequence motifs, GCAGA(A/T)C and CCCA(C/G)GAC. These sequences were found on chromosome 8 at the 5′ flanking site of the breakpoint junction of chromosome 8 in the TCR γ/δ leukemic cells reported here and also on chromosome 1 in T-cell acute lymphocytic leukemia patients carrying the t(1;14)(p32;q11) rearrangement. These results suggest that (i) during early stages of γδ T-cell ontogeny, the region 280 kb 3′ of the c-myc proto-oncogene on chromosome 8 is fragile and accessible to the lymphoid recombination machinery and (ii) rearrangements to both 8q24 and 1p32 may be governed by novel sequence motifs and be subject to common enzymatic mechanisms.