Evidence of a New Chimeric<i>bcr</i>/c-<i>abl</i>mRNA in Patients with Chronic Myelocytic Leukemia and the Philadelphia Chromosome

TLDR

The Philadelphia chromosome, a hallmark of chronic myelocytic leukemia, translocates the c‑abl oncogene from chromosome 9 to 22, where the breakpoint cluster region (bcr) is truncated, suggesting a role for this region in disease pathogenesis. The study aimed to test whether the deleted bcr region is replaced by c‑abl sequences by analyzing RNA from five chronic myelocytic leukemia patients. RNA from five chronic myelocytic leukemia patients was examined to detect chimeric bcr/c‑abl transcripts. All five patients expressed chimeric bcr/c‑abl mRNA, indicating that the disease’s deleterious effects may be linked to an abnormal chimeric protein encoded by bcr and c‑abl.

Abstract

The hallmark of chronic myelocytic leukemia is the presence of the Philadelphia chromosome (Ph1). In recent studies, we obtained data that strongly suggested the involvement of an oncogene, c-abl, in this type of leukemia. This oncogene, normally located on chromosome 9, is translocated to chromosome 22 as a result of the Ph1 translocation. In addition, we identified a region on chromosome 22, the breakpoint cluster region (bcr), which contains the chromosomal breakpoint in all patients with chronic myelocytic leukemia who are positive for Ph1. Recent studies have suggested that the bcr is part of a gene that is truncated as a consequence of the Ph1 translocation. The deleted part of this gene could be replaced by c-abl sequences; to test this hypothesis we analyzed the RNA of five patients with chronic myelocytic leukemia. All five had chimeric bcr/c-abl messenger RNA, suggesting that the deleterious effects of this disease can be associated with an abnormal chimeric protein encoded by the bcr and the c-abl oncogene.