Heterogeneity in expression of the bcr-abl fusion transcript in CML blast crisis

The 9;22 Philadelphia chromosome translocation in chronic myelogenous leukemia (CML) generates a bcr-abl fusion gene which codes for an aberrant 8-kb bcr-abl hybrid message. CML blast crisis cell lines display enhanced in vitro expression of this aberrant bcr-abl transcript when compared with fresh CML chronic phase cells. We directly compared in fresh patient samples the level of expression of the bcr-abl transcript in CML blast crisis versus chronic phase cells. All chronic phase patients displayed relatively low amounts of this aberrant transcript, while four of 10 blast crisis patients expressed this transcript at significantly higher levels. The remaining six blast crisis samples exhibited low levels of the aberrant transcript comparable to chronic phase cells. The two patients displaying the highest levels of the bcr-abl transcript did not harbor amplified copies of the bcr-abl fusion gene. This heterogeneity in the level of expression of the bcr-abl transcript in CML blast crisis indicates that enhanced expression of this aberrant transcript is not an absolutely necessary condition for blast transformation.