Clinical Relevance of a Pharmacogenetic Approach Using Multiple Candidate Genes to Predict Response and Resistance to Imatinib Therapy in Chronic Myeloid Leukemia
Autor: | Suzanne Kamel-Reid, Xiangdong Liu, D.H. Kim, Jeffrey H. Lipton, Wei Xu, Hans A. Messner, Lakshmi Sriharsha, Katherine A. Siminovitch |
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Rok vydání: | 2009 |
Předmět: |
Adult
Male Cancer Research ATP Binding Cassette Transporter Subfamily B Adolescent Genotype medicine.drug_class Fusion Proteins bcr-abl Antineoplastic Agents Biology Polymorphism Single Nucleotide Piperazines Tyrosine-kinase inhibitor Young Adult Gene Frequency Leukemia Myelogenous Chronic BCR-ABL Positive hemic and lymphatic diseases medicine ATP Binding Cassette Transporter Subfamily G Member 2 Cytochrome P-450 CYP3A Humans Genetic Predisposition to Disease ATP Binding Cassette Transporter Subfamily B Member 1 Aged Glycoproteins ABL Myeloid leukemia Imatinib Middle Aged Prognosis medicine.disease Neoplasm Proteins Pyrimidines Treatment Outcome Imatinib mesylate Oncology Drug Resistance Neoplasm Pharmacogenetics Benzamides Imatinib Mesylate Cancer research ATP-Binding Cassette Transporters Female Tyrosine kinase Octamer Transcription Factor-1 Chronic myelogenous leukemia medicine.drug |
Zdroj: | Clinical Cancer Research. 15:4750-4758 |
ISSN: | 1557-3265 1078-0432 |
Popis: | Purpose: Imatinib resistance is major cause of imatinib mesylate (IM) treatment failure in chronic myeloid leukemia (CML) 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, α1-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. |
Databáze: | OpenAIRE |
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