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Blood, 15 September 2001, Vol. 98, No. 6, pp. 1732-1738
CLINICAL OBSERVATIONS, INTERVENTIONS, AND THERAPEUTIC TRIALS
Deletions of the derivative chromosome 9 occur at the time of the
Philadelphia translocation and provide a powerful and independent
prognostic indicator in chronic myeloid leukemia
Brian J. P. Huntly,
Alistair G. Reid,
Anthony J. Bench,
Lynda J. Campbell,
Nick Telford,
Patricia Shepherd,
Jeff Szer,
H. Miles Prince,
Paul Turner,
Colin Grace,
Elizabeth P. Nacheva, and
Anthony R. Green
From the Department of Hematology, University of
Cambridge, Cambridge, United Kingdom; Victorian Cancer Cytogenetic
Service, St Vincent Hospital, Fitzroy, Australia; Oncology Cytogenetics
Service, Christie Hospital, Manchester, United Kingdom; Department of
Hematology, Western General Hospital, Edinburgh, United Kingdom;
Department of Clinical Hematology and Medical Oncology, Royal
Melbourne Hospital, Melbourne, Australia;Department of Hematology,
Peter Macallum Cancer Institute, Melbourne, Australia;Department of
Hematology, Alfred Hospital, Melbourne, Australia; and Digital
Scientific, Cambridge, United Kingdom.
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.
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