There is increasing evidence for a relationship between specific genom
ic alterations and the distinctive features of leukemia, including the
course and the response to treatment. In Philadelphia (Ph) positive c
hronic myeloid leukemia (CML) the BCR/ABL fusion genes can be transcri
bed in at least two different mRNAs that can either include (a2b3) or
exclude (a2b2) the exon 3 of the major breakpoint cluster region in ch
romosome 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 y
ear, and were followed for 39 to 84 months (median 60 months). The tra
nscript 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 af
ter 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 differe
nces were not significant, and we conclude that the identification of
the transcript type by current methodology does not predict for respon
se to alpha-IFN and for prognosis. Further studies may be required to
confirm that conclusion, or to detect a true smaller difference.