Differential expression of bcr/abl mRNA as determined by in situ amplification as s marker of disease progression in CMLs

In situ amplification of bcr/abl mRNA in individual cells of blood and bone marrow allows to detect cells carrying the bcr/abl trans-location typical for CML and transcribing the fusion mRNA. Using hybridization with a fluorochrome labeled probe the signal can be quantified as an indicator of trancritptional activity of individual cells. In 22 patients with CML the detection of positive cells by in situ amplification correlated well with cytogenetic results (r= 0.94). In two patients bcr/abl positive cells were detected in complete cytogenetic remission, bcr/abl mRNA was no longer detectable in three initially positive patients upon (treatment despite of cytogenetics still showing 100% Ph+ metaphases indicating transcriptional down-regulation. Semiquantitative analysis of bcr/abl mRNA showed the highest expression in patients with CML résistent to IFN treatment and in remnant leukemic cells of patients sensitive to treatment. Thus analysis of bcr/abl rearrangement at the single cell level detects early relapse in CML patients and monitoring of the expression of the fusion mRNA indicates that cells with different levels of expression are differently sensitive to treatment.