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Blood, 1 March 2005, Vol. 105, No. 5, pp. 2093-2098. Prepublished online as a Blood First Edition Paper on September 2, 2004; DOI 10.1182/blood-2004-03-1114. This Article Full Text (PDF) All Versions of this Article: 2004-03-1114v1 105/5/2093    most recent Alert me when this article is cited Alert me if a correction is posted 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 Chu, S. Articles by Bhatia, R. Search for Related Content PubMed PubMed Citation Articles by Chu, S. Articles by Bhatia, R. Related Collections Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted March 24, 2004 Accepted August 21, 2004 Detection of BCR-ABL kinase mutations in CD34+ cells from chronic myelogenous leukemia patients in complete cytogenetic remission on imatinib mesylate treatment Su Chu, Helen Xu, Neil P Shah, David S Snyder, Stephen J Forman, Charles L Sawyers, and Ravi Bhatia* Division of Hematology and Hematopoietic Cell Transplantation, City of Hope National Medical Center, Duarte, CA, USA Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, CA, USA * Corresponding author; email: rbhatia{at}coh.org. The BCR-ABL kinase inhibitor imatinib mesylate induces complete cytogenetic responses (CCR) in a high proportion of chronic myelogenous leukemia (CML) patients. However patients in CCR usually demonstrate evidence of residual BCR-ABL+ progenitors. The mechanisms underlying persistence of small numbers of malignant progenitors in imatinib-sensitive patients are unclear. BCR-ABL kinase domain mutations affecting drug binding can lead to secondary resistance to imatinib. We show here that kinase mutations could be detected in CD34+ cells isolated from CML patients in CCR on imatinib. The majority of mutations seen have not been reported in previous clinical studies. Interestingly several of the involved amino acid positions have been implicated in an in vitro mutagenesis screen. These BCR-ABL mutations were associated with varying levels of imatinib resistance. Two of five patients in whom mutations were detected on initial evaluation have relapsed. In addition four patients in whom mutations were not initially detected, but with rising BCR-ABL mRNA levels on Q-PCR analysis, had mutations detected on follow up evaluation. We conclude that BCR-ABL kinase mutations can be detected in CD34+ cells from CML patients in CCR on imatinib, may contribute to persistence of small populations of malignant progenitors, and could be a potential source of relapse. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: Can we afford to let sleeping dogs lie? Michael W. N. Deininger and Tessa L. Holyoake Blood 2005 105: 1840-1841. [Full Text] [PDF] This article has been cited by other articles: J. Abraham, M. Edgerly, R. Wilson, C. Chen, A. Rutt, S. Bakke, R. Robey, A. Dwyer, B. Goldspiel, F. Balis, et al. A Phase I Study of the P-Glycoprotein Antagonist Tariquidar in Combination with Vinorelbine Clin. Cancer Res., May 15, 2009; 15(10): 3574 - 3582. [Abstract] [Full Text] [PDF] D. Jones, S. Kamel-Reid, D. Bahler, H. Dong, K. Elenitoba-Johnson, R. Press, N. Quigley, P. Rothberg, D. Sabath, D. Viswanatha, et al. 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