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
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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