Absence of alternative splicing in bcr-abl mRNA in chronic myeloid leukemia cell lines

Abstract

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 P210(bcr-abl). In contrast to this, in Ph chromosome-positive acute lymphoblastic leukemia (Ph + ALL), a P190(bcr-abl) can be observed. This P190(bcr-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 P210(bcr-abl) into P190(bcr-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.