IJMEG Copyright © 2010-present. All rights reserved. Published by e-Century Publishing Corporation, Madison, WI 53711
Int J Mol Epidemiol Genet 2010;1(3):201-207.

Original Article
Genetic polymorphisms of ATP-binding cassette (ABC) proteins, overall
survival and drug toxicity in patients with Acute Myeloid Leukemia

Shalaka S. Hampras, Lara Sucheston, Joli Weiss, Maria R. Baer, Gary Zirpoli, Prashant K. Singh,
Meir Wetzler, Raj Chennamaneni, Javier G. Blanco, LaurieAnn Ford, Kirsten B. Moysich

Dept. of Neurology, University of Milan, Ospedale L. Sacco, Milan, Italy; Dept. of Neurological Sciences, "Dino
Ferrari" Center, University of Milan, IRCCS Ospedale Maggiore Policlinico, Milan, Italy; Dept. of Neuroscience, Istituto
di Ricerche Farmacologiche “Mario Negri”, Milan, Italy; Section of Biochemistry, Faculty of Medicine, University of
Brescia and III Laboratorio Analisi Chimico Cliniche, Spedali Civili di Brescia, Brescia, Italy; University of Maryland
Greenebaum Center, Baltimore, MD, 21201, USA; Department of Medicine, Roswell Park Cancer Institute, Buffalo,
NY, 14263, USA; Department of Pharmaceutical Sciences, University at Buffalo, NY, 14214, USA; Department of
Clinical Research Services, Roswell Park Cancer Institute, Buffalo, NY, 14263, USA.

Received April 18, 2010, accepted May 17, 2010, available online May 20, 2010

Abstract: The overall survival of patients with acute myeloid leukemia (AML) remains poor due to both intrinsic and
acquired chemotherapy resistance. Over expression of ATP binding cassette (ABC) proteins in AML cells has been
suggested as a putative mechanism of drug resistance. Genetic variation among individuals affecting the expression
or function of these proteins may contribute to inter-individual variation in treatment outcomes. DNA from pretreatment
bone marrow or blood samples from 261 patients age 20-85 years, who received cytarabine and anthracycline-
based therapy at Roswell Park Cancer Institute between 1994 and 2006, was genotyped for eight nonsynonymous
single nucleotide polymorphisms in the ABCB1, ABCC1 and ABCG2 drug transporter genes. Heterozygous
(AG) or homozygous (AA) variant genotypes for rs2231137 (G34A) in the ABCG2 (BRCP) gene, compared to the
wild type (GG) genotype were associated with both significantly improved survival (HR=0.44, 95%CI=0.25-0.79), and
increased odds for toxicity (OR=8.41, 95%CI=1.10-64.28). Thus genetic polymorphisms in the ABCG2 (BRCP) gene
may contribute to differential survival outcomes and toxicities in AML patients via a mechanism of decreased drug
efflux in both, AML cells and normal progenitors. (IJMEG1004002).

Keywords: Acute myeloid leukemia, multidrug resistance, polymorphisms, survival, toxicity

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Address all correspondence to:
Kirsten B. Moysich, PhD
Professor of Oncology
Roswell Park Cancer Institute
Buffalo, NY, 14263, USA.
Tel: 716-845 8004
E-mail:
Kirsten.Moysich@RoswellPark.org