Chronic myeloid leukemia (CML) is characterized by formation of a BCR-ABL fusion 
gene, usually as a consequence of the Philadelphia (Ph) translocation between 
chromosomes 9 and 22. Recently the development of new fluorescence in-situ 
hybridization (FISH) techniques has allowed identification of unexpected 
deletions of the reciprocal translocation product, the derivative chromosome 9, 
in 10% to 15% of patients with CML. These deletions are large, span the 
translocation breakpoint, and occur at the same time as the Ph translocation. 
Such deletions therefore give rise to previously unsuspected molecular 
heterogeneity from the very beginning of this disease, and there is mounting 
evidence for similar deletions associated with other translocations. Several 
studies have demonstrated that CML patients who carry derivative chromosome 9 
deletions exhibit a more rapid progression to blast crisis and a shorter 
survival. Deletion status is independent of, and more powerful than, the Sokal 
and Hasford/European prognostic scoring systems. The poor prognosis associated 
with deletions is seen in patients treated with hydroxyurea or interferon, and 
preliminary evidence suggests that patients with deletions may also have a worse 
outcome than nondeleted patients following stem cell transplantation or 
treatment with imatinib. Poor outcome cannot be attributed to loss of the 
reciprocal ABL-BCR fusion gene expression alone, and is likely to reflect loss 
of one or more critical genes within the deleted region. The molecular 
heterogeneity associated with the Philadelphia translocation provides a new 
paradigm with potential relevance to all malignancies associated with reciprocal 
chromosomal translocations and/or fusion gene formation.