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Blood, 3 September 2009, Vol. 114, No. 10, pp. 2168-2171. Prepublished online as a Blood First Edition Paper on July 9, 2009; DOI 10.1182/blood-2009-01-197186. This Article Full Text Full Text (PDF) Supplemental Figures All Versions of this Article: blood-2009-01-197186v1 114/10/2168    most recent 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 CrossRef Google Scholar Articles by Soverini, S. Articles by Martinelli, G. PubMed PubMed Citation Articles by Soverini, S. Articles by Martinelli, G. Related Collections Myeloid Neoplasia Brief Reports Clinical Trials and Observations Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  MYELOID NEOPLASIA Brief report Philadelphia-positive patients who already harbor imatinib-resistant Bcr-Abl kinase domain mutations have a higher likelihood of developing additional mutations associated with resistance to second- or third-line tyrosine kinase inhibitors Simona Soverini1, Alessandra Gnani1, Sabrina Colarossi1, Fausto Castagnetti1, Elisabetta Abruzzese2, Stefania Paolini1, Serena Merante3, Ester Orlandi3, Silvia de Matteis4, Antonella Gozzini5, Ilaria Iacobucci1, Francesca Palandri1, Gabriele Gugliotta1, Cristina Papayannidis1, Angela Poerio1, Marilina Amabile1, Daniela Cilloni6, Gianantonio Rosti1, Michele Baccarani1, and Giovanni Martinelli1 1 Department of Hematology and Oncological Sciences L e A Seràgnoli, University of Bologna, Bologna; 2 Department of Hematology, University of Rome Tor Vergata, Rome; 3 Division of Hematology, Policlinico S Matteo, Pavia; 4 Department of Hematology, Università Cattolica Sacro Cuore, Rome; 5 Hematology Unit, Careggi, University of Florence, Florence; and 6 Department of Clinical and Biological Sciences, University of Turin, Turin, Italy Dasatinib and nilotinib are tyrosine kinase inhibitors (TKIs) developed to overcome imatinib resistance in Philadelphia-positive leukemias. To assess how Bcr-Abl kinase domain mutation status evolves during sequential therapy with these TKIs and which mutations may further develop and impair their efficacy, we monitored the mutation status of 95 imatinib-resistant patients before and during treatment with dasatinib and/or nilotinib as second or third TKI. We found that 83% of cases of relapse after an initial response are associated with emergence of newly acquired mutations. However, the spectra of mutants conferring resistance to dasatinib or nilotinib are small and nonoverlapping, except for T315I. Patients already harboring mutations had higher likelihood of relapse associated with development of further mutations compared with patients who did not harbor mutations (23 of 51 vs 8 of 44, respectively, for patients who relapsed on second TKI; 13 of 20 vs 1 of 6, respectively, for patients who relapsed on third TKI). CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

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