Clustering of breakpoints on chromosome 10 in acute T-cell leukemias with the t(10;14) chromosome translocation.

AUTOR(ES)

Kagan, J

RESUMO

The T-cell receptor (TCR) alpha/delta chain locus on chromosome 14q11 is nonrandomly involved in translocations and inversions in human T-cell neoplasms. We have analyzed three acute T-lymphoblastic leukemia samples carrying a t(10;14)(q24;q11) chromosome translocation by means of somatic cell hybrids and molecular cloning. In all cases studied the translocation splits the TCR delta chain locus. Somatic cell hybrids containing the human 10q+ chromosome resulting from the translocation retain the human terminal deoxynucleotidyltransferase gene mapped at 10q23-q24 and the diversity and joining, D delta 2-J delta 1, regions of the TCR delta chain, but not the V alpha region (variable region of the TCR alpha chain), demonstrating that the split occurred within the V alpha-D delta 2 region. Molecular cloning of the breakpoint junctions revealed that the TCR delta chain sequences involved are made from the D delta 2 segment. The chromosome breakpoints are clustered within a region of approximately 263 base pairs of chromosome 10. The results suggest that the translocation of the TCR delta chain locus to a locus on 10q, which we have designated TCL3, results in deregulation of this putative oncogene, leading to acute T-cell leukemia.

Documentos Relacionados

• Alpha-chain locus of the T-cell antigen receptor is involved in the t(10;14) chromosome translocation of T-cell acute lymphocytic leukemia.
• 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.
• Human T-cell tumours containing chromosome 14 inversion or translocation with breakpoints proximal to immunoglobulin joining regions at 14q32.
• S1 nuclease hypersensitive sites in an oligopurine/oligopyrimidine DNA from the t(10;14) breakpoint cluster region.
• Molecular involvement of the pvt-1 locus in a gamma/delta T-cell leukemia bearing a variant t(8;14)(q24;q11) translocation.