QUANTITATIVE MOLECULAR METHODS TO MONITOR THE RESPONSE OF CML PATIENTS TO INTERFERON-ALPHA

Interferon-alpha (IFN-alpha) induces cytogenetic responses of variable degree in patients with CML. We sought to establish the relationship between BCR-ABL transcript numbers measured by competitive two-step re verse transcription polymerase chain reaction (RT-PCR) and cytogenetic status in CML patients treated with IFN-alpha. All 305 samples from 1 33 patients investigated by RT-PCR were positive for BCR-ABL transcrip ts. In order to standardize results for variability in RNA and cDNA qu ality, we quantified total ABL transcripts in each sample as an intern al control. The BCR-ABL:ABL ratios correlated well with the cytogeneti c results. Quantitative nested PCR allowed the detection of residual B CR-ABL transcripts in all complete cytogenetic responders on IFN-alpha . We conclude that competitive PCR with internal controls is a reliabl e method for monitoring patients on IFN-alpha and reduces the need for repeated marrow investigations.