The chromosome translocation (11;14)(p13;q11) associated with T-cell acute lymphocytic leukemia: An 11p13 breakpoint cluster region

The translocation (11;14)(q13;q11) was observed in karyotypes of leukemic cells from a 3-year-old boy with T-cell acute lymphocytic leukemia (T-ALL). Since this translocation is a recurrent marker of T-ALL, we undertook to investigate its mode of formation and role in leukemogenesis. The cytogenetic breakpoint on chromosome 14 occurs in 14q11, the same band wherein lies the T-cell receptor α/δ chain gene; and Southern hybridization analysis of peripheral blood and bone marrow DNA uncovered a tumor-specific rearrangement in the D(δ)-J(δ) region of this locus. DNA encompassing the rearrangement was isolated by molecular cloning, and further analysis revealed it to be the t(11;14)(p13;q11) junction. Nucleotide sequence determination of the junction indicates that the 14q11 breakpoint occurs immediately adjacent to the D(δ)2 gene segment. Hence, the translocation arose as an aberrant rearrangement between the downstream recombination signal of D(δ)2 and a pseudo recombination signal adjacent to the chromosome 11 breakpoint. Finally, comparison of the breakpoint in band 11p13 with those of other translocations (11;14)(p13;q11) identified a breakpoint cluster region of ~ 1.2 kilobasepairs (kb), alterations of which may promote the development of T-ALL.