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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 Hofmann, W.-K. Articles by Koeffler, H. P. Search for Related Content PubMed PubMed Citation Articles by Hofmann, W.-K. Articles by Koeffler, H. P. Related Collections Oncogenes and Tumor Suppressors Brief Reports Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  Blood, 1 March 2002, Vol. 99, No. 5, pp. 1860-1862 BRIEF REPORT Ph+ acute lymphoblastic leukemia resistant to the tyrosine kinase inhibitor STI571 has a unique BCR-ABL gene mutation Wolf-K. Hofmann, Letetia C. Jones, Nathan A. Lemp, Sven de Vos, Harald Gschaidmeier, Dieter Hoelzer, Oliver G. Ottmann, and H. Phillip Koeffler From the Division of Hematology/Oncology, Cedars Sinai Research Institute, and Department of Pathology, UCLA School of Medicine, Los Angeles, California; Department of Hematology, University Hospital, Frankfurt am Main, Germany; Novartis Pharma AG, Nürnberg, Germany. The tyrosine kinase inhibitor STI571 is a promising agent for the treatment of advanced Philadelphia chromosome positive (Ph+) acute lymphoblastic leukemia (ALL), but resistance develops rapidly in most patients after an initial response. To identify mechanisms of resistance to STI571, 30 complementary DNAs (including 9 matched samples) obtained from the bone marrow of individuals with Ph+ ALL were analyzed by direct sequencing of a 714-base pair region of ABL encoding for the adenosine triphosphate (ATP)-binding site and the kinase activation loop. A single point mutation was found at nucleotide 1127 (GI6382056) resulting in Glu255Lys. This mutation occurred in 6 of 9 patients (67%) following their treatment with STI571 but not in the samples from patients before beginning treatment with STI571. Glu255Lys is within the motif important for forming the pocket of the ATP-binding site in ABL and it is highly conserved across species. In conclusion, Ph+ ALL samples resistant to STI571 have a unique mutation Glu255Lys of BCR-ABL. © 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: N. Godin-Heymann, I. Bryant, M. N. Rivera, L. Ulkus, D. W. Bell, D. J. Riese II, J. Settleman, and D. A. Haber Oncogenic Activity of Epidermal Growth Factor Receptor Kinase Mutant Alleles Is Enhanced by the T790M Drug Resistance Mutation Cancer Res., August 1, 2007; 67(15): 7319 - 7326. [Abstract] [Full Text] [PDF] H. Pfeifer, B. 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