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.

Profiling of drug-metabolizing enzymes/transporters in CD33+ acute myeloid leukemia patients treated with Gemtuzumab-Ozogamicin and Fludarabine, Cytarabine and Idarubicin / Iacobucci I.; Lonetti A.; Candoni A.; Sazzini M.; Papayannidis C.; Formica S.; Ottaviani E.; Ferrari A.; Michelutti A.; Simeone E.; Astolfi A.; Abbenante M.C.; Parisi S.; Cattina F.; Malagola M.; Russo D.; Damiani D.; Gherlinzoni F.; Gottardi M.; Baccarani M.; Fanin R.; Martinelli G.. - In: PHARMACOGENOMICS JOURNAL. - ISSN 1470-269X. - ELETTRONICO. - 13:4(2013), pp. 335-341. [10.1038/tpj.2012.13]

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

IACOBUCCI, ILARIA;LONETTI, ANNALISA;SAZZINI, MARCO;PAPAYANNIDIS, CRISTINA;FORMICA, SERENA;OTTAVIANI, EMANUELA;FERRARI, ANNA;ASTOLFI, ANNALISA;ABBENANTE, MARIACHIARA;PARISI, SARAH;CATTINA, FEDERICA;MALAGOLA, MICHELE;BACCARANI, MICHELE;MARTINELLI, GIOVANNI
2013

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.
2013
Profiling of drug-metabolizing enzymes/transporters in CD33+ acute myeloid leukemia patients treated with Gemtuzumab-Ozogamicin and Fludarabine, Cytarabine and Idarubicin / Iacobucci I.; Lonetti A.; Candoni A.; Sazzini M.; Papayannidis C.; Formica S.; Ottaviani E.; Ferrari A.; Michelutti A.; Simeone E.; Astolfi A.; Abbenante M.C.; Parisi S.; Cattina F.; Malagola M.; Russo D.; Damiani D.; Gherlinzoni F.; Gottardi M.; Baccarani M.; Fanin R.; Martinelli G.. - In: PHARMACOGENOMICS JOURNAL. - ISSN 1470-269X. - ELETTRONICO. - 13:4(2013), pp. 335-341. [10.1038/tpj.2012.13]
Iacobucci I.; Lonetti A.; Candoni A.; Sazzini M.; Papayannidis C.; Formica S.; Ottaviani E.; Ferrari A.; Michelutti A.; Simeone E.; Astolfi A.; Abbenante M.C.; Parisi S.; Cattina F.; Malagola M.; Russo D.; Damiani D.; Gherlinzoni F.; Gottardi M.; Baccarani M.; Fanin R.; Martinelli G.
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11585/128210
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