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This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Huntly, B. J. P. Articles by Green, A. R. Search for Related Content PubMed PubMed Citation Articles by Huntly, B. J. P. Articles by Green, A. R. Related Collections Neoplasia Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  Blood, 15 June 2002, Vol. 99, No. 12, pp. 4547-4553 NEOPLASIA Derivative chromosome 9 deletions in chronic myeloid leukemia: poor prognosis is not associated with loss of ABL-BCR expression, elevated BCR-ABL levels, or karyotypic instability Brian J. P. Huntly, Anthony J. Bench, Eric Delabesse, Alistair G. Reid, Juan Li, Mike A. Scott, Lynda Campbell, Jennie Byrne, Eleanor Pinto, Andre Brizard, Deitger Niedermeiser, Elizabeth P. Nacheva, Francois Guilhot, Michael Deininger, and Anthony R. Green From the Department of Hematology and the Applied Medical Statistics Department, University of Cambridge, United Kingdom; Victorian Cancer Cytogenetic Service, St Vincent Hospital, Fitzroy, Australia; the Department of Hematology, City Hospital, Nottingham, United Kingdom; the Department of Hematology, University Hospital, Poitiers, France; and the Department of Hematology, University Hospital, Leipzig, Germany. Deletions of the derivative chromosome 9 have recently been reported in chronic myeloid leukemia. These deletions are large, occur at the time of the Philadelphia (Ph) translocation, span the translocation breakpoint, and represent a powerful prognostic indicator. However, the molecular mechanisms responsible for the poor prognosis associated with deletions are obscure, and several possible models are investigated here. First, we demonstrate that all derivative chromosome 9 deletions detected by fluorescence in situ hybridization were associated with an absence of ABL-BCR expression. However, loss of ABL-BCR expression also occurred without an overt deletion, suggesting the existence of other mechanisms by which ABL-BCR transcription can be abolished. Furthermore, analysis of survival in 160 patients demonstrated that loss of ABL-BCR expression, in contrast to deletion status, was not an indicator of poor prognosis. Second, we addressed the possibility that concomitant small deletions of the Ph chromosome modulate BCR-ABL transcription. Real-time reverse-transcription polymerase chain reaction was used to demonstrate that derivative chromosome 9 deletions were not accompanied by altered levels of BCR-ABL transcripts. Third, deletions may represent a consequence of genetic instability within the target cell at the time of the Ph translocation, with the poor prognosis reflecting a predisposition to subsequent additional genetic alterations. However, patients with deletions do not exhibit an increased frequency of secondary cytogenetic changes following disease progression. Taken together, these data support a model in which deletions of the derivative chromosome 9 result in rapid disease progression as a result of the loss of one or more genes within the deleted region. © 2002 by The American Society of Hematology.   CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: S. Kreil, M. Pfirrmann, C. Haferlach, K. Waghorn, A. Chase, R. Hehlmann, A. Reiter, A. Hochhaus, N. C. P. 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