Hermans A, Heisterkamp N, von Linden M, van Baal S, Meijer D, van der Plas D, Wiedemann L M, Groffen J, Bootsma D, Grosveld G
Department of Cell Biology and Genetics Erasmus University, Rotterdam, The Netherlands.
Cell. 1987 Oct 9;51(1):33-40. doi: 10.1016/0092-8674(87)90007-9.
The Philadelphia (Ph) chromosome, the product of t(9:22), is the cytogenetic hallmark of chronic myelogenous leukemia. The c-abl oncogene on chromosome 9 is translocated to the Ph chromosome and linked to a breakpoint cluster region (bcr), which is part of a large bcr gene. This results in the formation of a bcr-c-abl fusion gene, which is transcribed into an 8.5 kb chimeric mRNA encoding a 210 kd bcr-c-abl fusion protein. The Ph chromosome is also found in acute lymphoblastic leukemia (Ph+ ALL). Although the c-abl is translocated and a new 190 kd c-abl protein has been identified, no breakpoints are observed in the bcr (Ph+bcr- ALL). Here we show that in Ph+bcr- ALL, breakpoints in chromosome 22 occur within the same bcr gene, but more 5' of the bcr. Cloning of a chimeric bcr-c-abl cDNA demonstrates that the fusion gene is transcribed into a 7 kb mRNA, encoding a novel fusion protein.
费城（Ph）染色体是9号和22号染色体易位的产物，是慢性粒细胞白血病的细胞遗传学标志。9号染色体上的c-abl原癌基因易位至Ph染色体，并与一个断裂簇区域（bcr）相连，该区域是一个大的bcr基因的一部分。这导致形成一个bcr-c-abl融合基因，该基因转录成一个8.5 kb的嵌合mRNA，编码一个210 kd的bcr-c-abl融合蛋白。Ph染色体也见于急性淋巴细胞白血病（Ph+ ALL）。虽然c-abl发生了易位，并且已鉴定出一种新的190 kd的c-abl蛋白，但在bcr中未观察到断裂点（Ph+bcr- ALL）。在此我们表明，在Ph+bcr- ALL中，22号染色体上的断裂点发生在同一个bcr基因内，但在bcr的更5'端。一个嵌合的bcr-c-abl cDNA的克隆表明，该融合基因转录成一个7 kb的mRNA，编码一种新的融合蛋白。
