Chronic myeloid leukemia (CML) is characterized by formation of the BCR-ABL 
fusion gene, usually as a consequence of the Philadelphia (Ph) translocation 
between chromosomes 9 and 22. Large deletions on the derivative chromosome 9 
have recently been reported, but it was unclear whether deletions arose during 
disease progression or at the time of the Ph translocation. Fluorescence in situ 
hybridization (FISH) analysis was used to assess the deletion status of 253 
patients with CML. The strength of deletion status as a prognostic indicator was 
then compared to the Sokal and Hasford scoring systems. The frequency of 
deletions was similar at diagnosis and after disease progression but was 
significantly increased in patients with variant Ph translocations. In patients 
with a deletion, all Ph(+) metaphases carried the deletion. The median survival 
of patients with and without deletions was 38 months and 88 months, respectively 
(P =.0001). By contrast the survival difference between Sokal or Hasford 
high-risk and non-high-risk patients was of only borderline significance (P 
=.057 and P =.034). The results indicate that deletions occur at the time of the 
Ph translocation. An apparently simple reciprocal translocation may therefore 
result in considerable genetic heterogeneity ab initio, a concept that is likely 
to apply to other malignancies associated with translocations. Deletion status 
is also a powerful and independent prognostic factor for patients with CML. The 
prognostic significance of deletion status should now be studied prospectively 
and, if confirmed, should be incorporated into management decisions and the 
analysis of clinical trials.