WILL MOLECULAR-BIOLOGY CONTRIBUTE TO REFINE PROGNOSIS AND TO SELECT TREATMENT

The possible prognostic value of the position of the breakpoint within the M-BCR in patients with Ph 1 + CML is still being debated. We analyzed the DNA rearrangements and the transcript types of 244 patients and tried to correlate the data obtained with prognostic features, defined according to Sokal's risk index, and with chronic phase and/or survival duration. The exact location of the breakpoint, either 5' or 3' to the Hind III restriction site within the M-BCR was identified. Moreover, the exact M-BCR subregion was also identified. As a whole, 150 pts were rearranged in the 5' part and 94 in the 3' part of the M-BCR. No correlation was observed between the site of rearrangement on the one hand and the Sokal's prognostic index and survival, on the other. Transcript analysis was performed in 130 patients; 59 carried an a2b2 and 69 an a,b3 pattern. Two patients carried both transcripts. Of the patients rearranged in the 5' area, according to Southern blotting, 29.2% showed an a,b3 transcript. Therefore, RT-PCR analysis allowed a better definition of the breakpoint. However, also the type of transcript did not show any correlation either with risk categories or survival. No difference in response to therapy, either chemotherapy or alpha interferon, was observed between 5' and 3' rearranged patients.