Molecular Cloning of the Chromosomal Breakpoint of B-Cell Lymphomas and Leukemias with the t(11;14) Chromosome Translocation

TLDR

The authors isolated a chromosome‑11–specific probe mapping immediately 5′ to the breakpoint on the translocated 14q chromosome. The breakpoint was cloned within the heavy‑chain joining segment on chromosome 14q, and a chromosome‑11 probe revealed a rearrangement specific to t(11;14) B‑cell malignancies, identifying a novel gene, bcl‑1, on 11q13 that is not related to known retroviral oncogenes.

Abstract

The chromosomal breakpoint of chronic lymphocytic leukemia (CLL) cells of the B-cell type carrying the translocated long arms of chromosomes 11 and 14 [t(11;14) (q13;q32)] was cloned. The breakpoint was found to be within the joining segment of the human heavy chain locus on the translocated long arm of chromosome 14. A probe that is specific for chromosome 11 and that maps immediately 5′ to the breakpoint on the 14q + chromosome was isolated. The probe detected a rearrangement of the homologous genomic DNA segment in the parental CLL cells and also in DNA from a diffuse large cell lymphoma with the t(11;14) translocation. This rearranged DNA segment was not present in Burkitt lymphoma cells with the t(8;14) translocation or in nonneoplastic human lymphoblastoid cells. The probe can thus be used to identify and characterize a gene located on band q13 of chromosome 11 that appears to be involved in the malignant transformation of human B cells carrying the t(11;14) translocation. This gene, named bcl-1 , appears to be unrelated to any of the known retrovirus oncogenes described to date.