Genetic polymorphisms of ATP-binding cassette (ABC) proteins, overall survival and drug toxicity in patients with Acute Myeloid Leukemia
作者： Gary Zirpoli , Kirsten B Moysich , Meir Wetzler , Lara Sucheston , Javier G Blanco
DOI:
关键词: Drug resistance 、 Cytarabine 、 Single-nucleotide polymorphism 、 ATP-binding cassette transporter 、 Cancer research 、 Genetic variation 、 Myeloid leukemia 、 Bone marrow 、 Genotype 、 Medicine 、 Pharmacology
摘要: The overall survival of patients with acute myeloid leukemia (AML) remains poor due to both intrinsic and acquired chemotherapy resistance. Over expression ATP binding cassette (ABC) proteins in AML cells has been suggested as a putative mechanism drug Genetic variation among individuals affecting the or function these may contribute inter-individual treatment outcomes. DNA from pre-treatment bone marrow blood samples 261 age 20-85 years, who received cytarabine anthracycline-based therapy at Roswell Park Cancer Institute between 1994 2006, was genotyped for eight non-synonymous single nucleotide polymorphisms ABCB1, ABCC1 ABCG2 transporter genes. Heterozygous (AG) homozygous (AA) variant genotypes rs2231137 (G34A) (BRCP) gene, compared wild type (GG) genotype were associated significantly improved (HR=0.44, 95%CI=0.25-0.79), increased odds toxicity (OR=8.41, 95%CI= 1.10-64.28). Thus genetic gene differential outcomes toxicities via decreased efflux both, normal progenitors.
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