Profiling of drug-metabolizing enzymes/transporters in CD33+ acute myeloid leukemia patients treated with Gemtuzumab-Ozogamicin and Fludarabine, Cytarabine and Idarubicin

The Pharmacogenomics Journal
Ilaria IacobucciGiovanni Martinelli

Abstract

Genetic heterogeneity in drug-metabolizing enzyme/transporter (DMET) genes affects specific drug-related cancer phenotypes. To investigate the relationships between genetic variation and response to treatment in acute myeloid leukemia (AML), we genotyped 1931 variants on DMET genes in 94 CD33-positive AML patients enrolled in a phase III multicenter clinical trial combining Gemtuzumab-Ozogamicin (GO) with Fludarabine-Cytarabine-Idarubicin (FLAI) regimen, with the DMET Plus platform. Two ADH1A variants showed statistically significant differences (odds ratio (OR)=5.68, P=0.0006; OR=5.35, P=0.0009) in allele frequencies between patients in complete/partial remission and patients without response, two substitutions on CYP2E1 (OR=0.13, P=0.001; OR=0.09, P=0.003) and one on SLCO1B1 (OR=4.68, P=0.002) were found to differently influence liver toxicity, and two nucleotide changes on SULTB1 and SLC22A12 genes correlated with response to GO (OR=0.24, P=0.0009; OR=2.75, P=0.0029). Genetic variants were thus found for the first time to be potentially associated with differential response and toxicity in AML patients treated with a combination of GO-FLAI regimen.

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Citations

Oct 26, 2012·BMC Bioinformatics·Vladan MijatovicGiovanni Malerba
Apr 8, 2014·Breast Cancer Research and Treatment·Daniel L HertzHoward L McLeod
Apr 27, 2010·Journal of Hematology & Oncology·Xiongpeng ZhuDelong Liu
Jun 18, 2016·International Journal of Cancer. Journal International Du Cancer·Lillian SungAlan S Gamis
Jul 7, 2016·Pharmacogenomics·Juan Eduardo Megías-VericatSalvador F Aliño
May 17, 2013·Journal of Human Genetics·Sook Wah YeeCharalambos Andreadis
Aug 2, 2013·Critical Ultrasound Journal·Maria Antonietta MazzeiLuca Volterrani
Sep 15, 2018·The Pharmacogenomics Journal·Jihoon ChoiQing Ling Duan
Sep 2, 2020·Expert Review of Hematology·Juan Eduardo Megías-VericatPau Montesinos
Aug 11, 2020·Expert Opinion on Drug Metabolism & Toxicology·Kateryna PetrykeyMaja Krajinovic
Dec 30, 2014·Physiological Reviews·Sanjay K NigamWei Wu
May 17, 2014·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Daniel L Hertz, Howard L McLeod

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