慢性粒细胞白血病和费城染色体患者中新型嵌合bcr/c-abl mRNA的证据。

Evidence of a new chimeric bcr/c-abl mRNA in patients with chronic myelocytic leukemia and the Philadelphia chromosome.

作者信息

Stam K, Heisterkamp N, Grosveld G, de Klein A, Verma R S, Coleman M, Dosik H, Groffen J

出版信息

N Engl J Med. 1985 Dec 5;313(23):1429-33. doi: 10.1056/NEJM198512053132301.

DOI:10.1056/NEJM198512053132301

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.

摘要

慢性粒细胞白血病的标志是费城染色体（Ph1）的存在。在最近的研究中，我们获得的数据强烈表明一种癌基因c-abl参与了这类白血病。这种癌基因通常位于9号染色体上，由于Ph1易位而转移到22号染色体上。此外，我们在22号染色体上鉴定出一个区域，即断裂点簇集区域（bcr），在所有Ph1阳性的慢性粒细胞白血病患者中，该区域都包含染色体断裂点。最近的研究表明，bcr是一个基因的一部分，该基因因Ph1易位而被截断。这个基因缺失的部分可以被c-abl序列取代；为了验证这一假设，我们分析了5例慢性粒细胞白血病患者的RNA。所有5例患者都有嵌合的bcr/c-abl信使RNA，这表明这种疾病的有害影响可能与bcr和c-abl癌基因编码的异常嵌合蛋白有关。