The t(10;14)(q24;q11) of T-cell acute lymphoblastic leukemia juxtaposes the delta T-cell receptor with TCL3, a conserved and activated locus at 10q24

M Zutter, R D Hockett, C W Roberts, E A McGuire, J Bloomstone, C C Morton, L L Deaven, W M Crist, A J Carroll, S J Korsmeyer

Research output: Contribution to journalArticlepeer-review

Abstract

We cloned the t(10;14) recurrent translocation from CD3-negative T-cell acute lymphoblastic leukemia cells. The breakpoint at 14q11 involved an intermediate rearrangement of the delta T-cell receptor locus, suggesting that the translocation arose at the time of antigen receptor assemblage. Translocation introduced chromosome segment 10q24 as proven by hybridization of a breakpoint-derived probe to flow-sorted chromosomes and metaphase chromosomes. Two t(10;14) breakpoints were clustered within a 600-base-pair region of 10q24 but no heptamer-spacer-nonamer motifs resembling T-cell receptor/immunoglobulin rearrangement signals were noted at the breakpoint. A locus distinct from terminal deoxynucleotidyltransferase was found at 10q24. Evolutionarily conserved regions surrounding the 10q24 breakpoint were examined for transcriptional activity. A region telomeric to the 10q24 breakpoint, expected to translocate to the der(14) chromosome, recognized an abundant 2.9-kilobase RNA in a t(10;14) T-cell leukemia. This locus was not active in a variety of other normal and neoplastic T cells, arguing that it was deregulated by the introduction of the T-cell receptor. This locus is a candidate for a putative protooncogene, TCL3, involved in T-cell neoplasia.

Original languageEnglish
Pages (from-to)3161-5
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume87
Issue number8
Publication statusPublished - Apr 1990

Keywords

  • Alleles
  • Antigens, CD
  • Base Sequence
  • Chromosomes, Human, Pair 10
  • Chromosomes, Human, Pair 14
  • Cloning, Molecular
  • DNA, Neoplasm
  • Gene Rearrangement, T-Lymphocyte
  • Humans
  • Leukemia-Lymphoma, Adult T-Cell
  • Macromolecular Substances
  • Molecular Sequence Data
  • Receptors, Antigen, T-Cell
  • Restriction Mapping
  • Sequence Homology, Nucleic Acid
  • Translocation, Genetic
  • Tumor Cells, Cultured
  • Journal Article
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

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