Clinical Relevance of a Pharmacogenetic Approach Using Multiple Candidate Genes to Predict Response and Resistance to Imatinib Therapy in Chronic Myeloid Leukemia

被引:156
作者
Kim, Dong Hwan [1 ,2 ]
Sriharsha, Lakshmi [2 ]
Xu, Wei [3 ]
Kamel-Reid, Suzanne [4 ]
Liu, Xiangdong [5 ]
Siminovitch, Katherine [5 ]
Messner, Hans A. [2 ]
Lipton, Jeffrey H. [2 ]
机构
[1] Sungkyunkwan Univ, Dept Hematol Oncol, Samsung Med Ctr, Sch Med, Seoul 135710, South Korea
[2] Univ Toronto, Dept Med Hematol Oncol, Chron Myelogenous Leukemia Grp, Toronto, ON, Canada
[3] Univ Toronto, Princess Margaret Hosp, Dept Biostat, Toronto, ON, Canada
[4] Univ Toronto, Univ Hlth Network, Dept Pathol, Toronto, ON, Canada
[5] Univ Hlth Network, Analyt Genet Technol Ctr, Toronto, ON, Canada
关键词
SINGLE NUCLEOTIDE POLYMORPHISMS; HIGH-AFFINITY INTERACTION; CATION TRANSPORTER HOCT1; BCR-ABL TRANSCRIPTS; P-GLYCOPROTEIN; ALPHA-1-ACID GLYCOPROTEIN; MULTIDRUG-RESISTANCE; TYROSINE KINASE; OCT-1; ACTIVITY; MESYLATE;
D O I
10.1158/1078-0432.CCR-09-0145
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Purpose: Imatinib resistance is major cause of imatinib mesylate (IM) treatment failure in chronic myeloid leukemia (CIVIL) patients. Several cellular and genetic mechanisms of imatinib resistance have been proposed, including amplification and overexpression of the BCR/ABL gene, the tyrosine kinase domain point mutations, and MDR1 gene overexpression. Experimental Design: We investigated the impact of 16 single nucleotide polymorphisms (SNP) in five genes potentially associated with pharmacogenetics of IM, namely ABCB1, multidrug resistance 1; ABCG2, breast-cancer resistance protein; CYP3A5, cytochrome P450-3A5; SLC22A1, human organic cation transporter 1; and AGP, alpha 1-acid glycoprotein. The DNAs from peripheral blood samples in 229 patients were genotyped. Results: The GG genotype in ABCG2 (rs2231137), AA genotype in CYP3A5 (rs776746), and advanced stage were significantly associated with poor response to IM especially for major or complete cytogenetic response, whereas the GG genotype at SLC22A1 (rs683369) and advanced stage correlated with high rate of loss of response or treatment failure to IM therapy. Conclusions: We showed that the treatment outcomes of imatinib therapy could be predicted using a novel, multiple candidate gene approach based on the pharmacogenetics of IM.
引用
收藏
页码:4750 / 4758
页数:9
相关论文
共 46 条
[1]   Evolving concepts in the management of chronic myeloid leukemia: recommendations from an expert panel on behalf of the European LeukemiaNet [J].
Baccarani, Michele ;
Saglio, Giuseppe ;
Goldman, John ;
Hochhaus, Andreas ;
Simonsson, Bengt ;
Appelbaum, Frederick ;
Apperley, Jane ;
Cervantes, Francisco ;
Cortes, Jorge ;
Deininger, Michael ;
Gratwohl, Alois ;
Guilhot, Frangois ;
Horowitz, Mary ;
Hughes, Timothy ;
Kantarjian, Hagop ;
Larson, Richard ;
Niederwieser, Dielger ;
Silver, Richard ;
Hehlmann, Rudiger .
BLOOD, 2006, 108 (06) :1809-1820
[2]   Effect of rifampicin on the pharmacokinetics of imatinib mesylate (Gleevec, STI571) in healthy subjects [J].
Bolton, AE ;
Peng, B ;
Hubert, M ;
Krebs-Brown, A ;
Capdeville, R ;
Keller, U ;
Seiberling, M .
CANCER CHEMOTHERAPY AND PHARMACOLOGY, 2004, 53 (02) :102-106
[3]   Rationale for the recommendations for harmonizing current methodology for detecting BCR-ABL transcripts in patients with chronic myeloid leukaemia [J].
Branford, S. ;
Cross, N. C. P. ;
Hochhaus, A. ;
Radich, J. ;
Saglio, G. ;
Kaeda, J. ;
Goldman, J. ;
Hughes, T. .
LEUKEMIA, 2006, 20 (11) :1925-1930
[4]   Desirable performance characteristics for BCR-ABL measurement on an international reporting scale to allow consistent interpretation of individual patient response and comparison of response rates between clinical trials [J].
Branford, Susan ;
Fletcher, Linda ;
Cross, Nicholas C. P. ;
Mueller, Martin C. ;
Hochhaus, Andreas ;
Kim, Dong-Wook ;
Radich, Jerald P. ;
Saglio, Giuseppe ;
Pane, Fabrizio ;
Kamel-Reid, Suzanne ;
Wang, Y. Lynn ;
Press, Richard D. ;
Lynch, Kevin ;
Rudzki, Zbigniew ;
Goldman, John M. ;
Hughes, Timothy .
BLOOD, 2008, 112 (08) :3330-3338
[5]   Imatinib mesylate and nilotinib (AMN107) exhibit high-affinity interaction with ABCG2 on primitive hematopoietic stem cells [J].
Brendel, C. ;
Scharenberg, C. ;
Dohse, M. ;
Robey, R. W. ;
Bates, S. E. ;
Shukla, S. ;
Ambudkar, S. V. ;
Wang, Y. ;
Wennemuth, G. ;
Burchert, A. ;
Boudriot, U. ;
Neubauer, A. .
LEUKEMIA, 2007, 21 (06) :1267-1275
[6]   hOCT 1 and resistance to imatinib [J].
Crossman, LC ;
Druker, BJ ;
Deininger, MWN .
BLOOD, 2005, 106 (03) :1133-1134
[7]   Multidrug resistance mediated by the breast cancer resistance protein BCRP (ABCG2) [J].
Doyle, LA ;
Ross, DD .
ONCOGENE, 2003, 22 (47) :7340-7358
[8]   Efficacy and safety of a specific inhibitor of the BCR-ABL tyrosine kinase in chronic myeloid leukemia. [J].
Druker, BJ ;
Talpaz, M ;
Resta, DJ ;
Peng, B ;
Buchdunger, E ;
Ford, JM ;
Lydon, NB ;
Kantarjian, H ;
Capdeville, R ;
Ohno-Jones, S ;
Sawyers, CL .
NEW ENGLAND JOURNAL OF MEDICINE, 2001, 344 (14) :1031-1037
[9]   Pharmacokinetic interaction between ketoconazole and imatinib mesylate (Glivec) in healthy subjects [J].
Dutreix, C ;
Peng, B ;
Mehring, G ;
Hayes, M ;
Capdeville, R ;
Pokorny, R ;
Seiberling, M .
CANCER CHEMOTHERAPY AND PHARMACOLOGY, 2004, 54 (04) :290-294
[10]   Selective binding of imatinib to the genetic variants of human α1-acid glycoprotein [J].
Fitos, Ilona ;
Visy, Julia ;
Zsila, Ferenc ;
Mady, Gyorgy ;
Simonyi, Miklos .
BIOCHIMICA ET BIOPHYSICA ACTA-GENERAL SUBJECTS, 2006, 1760 (11) :1704-1712