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

Citation
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
Citations number
56
Categorie Soggetti
Hematology,"Cardiovascular & Hematology Research
Journal title
BLOOD
ISSN journal
00064971 → ACNP
Volume
98
Issue
6
Year of publication
2001
Pages
1732 - 1738
Database
ISI
SICI code
0006-4971(20010915)98:6<1732:DOTDC9>2.0.ZU;2-O
Abstract
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.