Detection of minimal residual bcr/abl transcripts by a modified polymerase chain reaction

The Philadelphia (Ph¹) chromosome in chronic myelogenous leukemia (CML) involves reciprocal translocation of the bcr gene and the c-abl oncogene. The fused bcr/abl gene is transcribed into two types of chimeric mRNA. By means of a combined method of S₁ nuclease protection and polymerase chain reaction, we amplified sequences representative of the chimeric bcr/abl transcripts. Only 5 μg of total cellular RNA is needed and the chimeric bcr/abl message can be detected at a dilution of 1:100,000. We also detected residual chimeric bcr/abl transcripts in the remission samples from two Ph¹-positive CML patients. This technique has the potential to identify a subpopulation of Ph¹-positive CML patients in remission who are at high risk of relapse.