Large deletions at the t(9;22) breakpoint are common and may identify a poor-prognosis subgroup of patients with chronic myeloid leukemia

The hallmark of chronic myeloid leukemia (CML) Is the BCR-ABL fusion gene, which is usually formed as a result of the t(9;22) translocation, Patients with CML show considerable heterogeneity both in their presenting clinical features and in the time taken for evolution to blast crisis, in this study , metaphase fluorescence in situ hybridization showed that a substantial mi nority of patients with CML had large deletions adjacent to the translocati on breakpoint on the derivative 9 chromosome, on the additional partner chr omosome in variant translocations, or on both. The deletions spanned up to several mega-bases, had variable breakpoints, and could be detected by micr osatellite polymerase chain reaction in unfractionated bone marrow and puri fied peripheral blood granulocytes, The deletions were likely to occur earl y and possibly at the time of the Philadelphia (Ph) chromosome translocatio n: deletions were detected at diagnosis in 11 patients, were found in all p h-positive metaphases, and were more prevalent in patients with variant Ph chromosomes. Kaplan-Meier analysis showed a median survival time of 36 mont hs in patients with a deletion; patients without a detectable deletion surv ived > 90 months. The survival-time difference was significant on log-rank analysis (P = .006), Multivariate analysis demonstrated that the prognostic importance of deletion status was independent of age, sex, percentage of p eripheral blood blasts, and platelet count. Our data therefore suggest that an apparently simple, balanced translocation may result not only In the ge neration of a dominantly acting fusion oncogene but also in the loss of one or more genes that influence disease progression. (C) 2000 by The American Society of Hematology.