Chronic myeloid leukemia, BCR/ABL transcript, response to alpha-interferon and survival. The Italian Cooperative...

There is increasing evidence for a relationship between specific genomic alterations and the distinctive features of leukemia, including the course and the response to treatment. In Philadelphia (Ph) positive chronic myeloid leukemia (CML) the BCR/ABL fusion genes can be transcribed in at least two different mRNAs that can either include (a2b3) or exclude (a2b2) the exon 3 of the major breakpoint cluster region in chromosome 22. We identified by polymerase chain reaction the transcript type in 146 patients with Ph+ CML who were enrolled in a prospective study of treatment with alpha-interferon (alpha-IFN) for at least 1 year, and were followed for 39 to 84 months (median 60 months). The transcript was a2b3 in 84 cases (57%) and a2b2 in 62 cases (43%). A trend in favor of a2b3 cases was observed, as to the karyotypic response after 1 year of alpha-IFN treatment (39% in the a2b3 cases vs 24% in the a2b2 cases) and 5-year survival rate, that was 71% (95% CI 59-82) in a2b3 cases vs 57% (95% CI 41-73) in a2b2 cases. However, these differences were not significant, and we conclude that the identification of the transcript type by current methodology does not predict for response to alpha-IFN and for prognosis. Further studies may be required to confirm that conclusion, or to detect a true smaller difference.