Hermans A, Gow J, Selleri L, von Lindern M, Hagemeijer A, Wiedemann L M, Grosveld G
Department of Cell Biology and Genetics, Erasmus University, Rotterdam, The Netherlands.
Leukemia. 1988 Oct;2(10):628-33.
Tumor-specific alterations in oncogenes are thought to play a central role in the development of cancer. An example is the consistent fusion of the bcr gene to the c-abl oncogene on the Ph chromosome in CML. The Ph chromosome can also be observed in ALL. About 50% of Ph+ ALL cases, in contrast to CML, do not exhibit chromosomal breakpoints in the major cluster region or mcr (Ph+ mcr- ALL). These cases may have a novel bcr-abl fusion gene instead. We tested this hypothesis in eight Ph+ mcr- ALL patients by amplifying the putative hybrid part of the bcr-abl cDNA, using the polymerase chain reaction method. All cases examined showed the same joining of the first exon of the bcr gene to the c-abl oncogene. Thus, the novel bcr-abl fusion in Ph+ mcr- ALL is the result of a molecularly distinct Ph chromosome. This allows the definition of Ph+ leukemias by their respective bcr-abl oncogene activation. Moreover, the cDNA amplification method we use is a clinically useful tool to screen for bcr-abl oncogene activations in leukemia patients.
致癌基因中的肿瘤特异性改变被认为在癌症发展中起核心作用。一个例子是慢性粒细胞白血病（CML）中第22号染色体（Ph染色体）上bcr基因与c-abl致癌基因的持续融合。在急性淋巴细胞白血病（ALL）中也可观察到Ph染色体。与CML相反，约50%的Ph+ ALL病例在主要簇集区域或mcr（Ph+ mcr- ALL）中未表现出染色体断点。这些病例可能具有一种新的bcr-abl融合基因。我们通过聚合酶链反应方法扩增bcr-abl cDNA的假定杂交部分，在8例Ph+ mcr- ALL患者中检验了这一假设。所有检测病例均显示bcr基因的第一个外显子与c-abl致癌基因的相同连接。因此，Ph+ mcr- ALL中的新型bcr-abl融合是分子上不同的Ph染色体的结果。这使得可以根据各自的bcr-abl致癌基因激活来定义Ph+白血病。此外，我们使用的cDNA扩增方法是一种在白血病患者中筛查bcr-abl致癌基因激活的临床有用工具。
