Molecular involvement of the pvt-1 locus in a γ/δ T-cell leukemia bearing a variant t(8;14)(q24;q11) translocation

M. Kasai, R. T. Maziarz, K. Aoki, E. Macintyre, J. L. Strominger

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Abstract

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.

Original languageEnglish (US)
Pages (from-to)4751-4757
Number of pages7
JournalMolecular and cellular biology
Volume12
Issue number10
StatePublished - Jan 1 1992

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ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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