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
Bjp. Huntly et al., 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, BLOOD, 98(6), 2001, pp. 1732-1738
Chronic myeloid leukemia (CML) is characterized by formation of the BCR-ABL
fusion gene, usually as a consequence of the Philadelphia (Ph) translocati
on between chromosomes 9 and 22. Large deletions on the derivative chromoso
me 9 have recently been reported, but it was unclear whether deletions aros
e during disease progression or at the time of the Ph translocation. Fluore
scence in situ hybridization (FISH) analysis was used to assess the deletio
n status of 253 patients with CML. The strength of deletion status as a pro
gnostic indicator was then compared to the Sokal and Hasford scoring system
s. The frequency of deletions was similar at diagnosis and after disease pr
ogression but was significantly increased in patients with variant Ph trans
locations. In patients with a deletion, all Ph+ metaphases carried the dele
tion. The median survival of patients with and without deletions was 38 mon
ths and 88 months, respectively (P = .0001). By contrast the survival diffe
rence 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 sim
ple reciprocal translocation may therefore result in considerable genetic h
eterogeneity ab initio, a concept that is likely to apply to other malignan
cies associated with translocations. Deletion status is also a powerful and
independent prognostic factor for patients with CML. The prognostic signif
icance of deletion status should now be studied prospectively and, if confi
rmed, should be incorporated into management decisions and the analysis of
clinical trials. (C) 2001 by The American Society of Hematology.