Hermans A, Selleri L, Gow J, Grosveld G C
Department of Cell Biology and Genetics, Erasmus University, Rotterdam, The Netherlands.
Blood. 1988 Dec;72(6):2066-9.
The major consequence of the Philadelphia (Ph) translocation in chronic myeloid leukemia (CML) is the formation of a bcr-abl hybrid oncogene encoding a tumor cell-specific protein P210bcr-abl. In contrast to this, in Ph chromosome-positive acute lymphoblastic leukemia (Ph + ALL), a P190bcr-abl can be observed. This P190bcr-abl has been implicated in acute rather than chronic leukemogenesis. Therefore, it can be hypothesized that the transition from chronic to blast phase in CML is accompanied by an alternative splice in the bcr-abl mRNA, which results in a switch of the production of P210bcr-abl into P190bcr-abl. Initial S1 nuclease protection mapping supported this theory. However, this result appears to be based on an artifact in the S1 analysis. By using the polymerase chain reaction we provide evidence for the absence of alternative splicing in bcr-abl mRNA in two CML blast crisis cell lines.
费城（Ph）染色体易位在慢性髓性白血病（CML）中的主要后果是形成一种bcr-abl融合癌基因，其编码一种肿瘤细胞特异性蛋白P210bcr-abl。与此相反，在Ph染色体阳性急性淋巴细胞白血病（Ph + ALL）中，可以观察到P190bcr-abl。这种P190bcr-abl与急性而非慢性白血病发生有关。因此，可以推测CML从慢性期向急变期的转变伴随着bcr-abl mRNA的可变剪接，这导致P210bcr-abl的产生转换为P190bcr-abl。最初的S1核酸酶保护图谱支持了这一理论。然而，这一结果似乎是基于S1分析中的一个假象。通过使用聚合酶链反应，我们提供了证据，证明在两个CML急变期细胞系中bcr-abl mRNA不存在可变剪接。
