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

Abstract

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 .apprxeq. 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.