Polymorphisms within methotrexate pathway genes: Relationship between plasma methotrexate levels, toxicity experienced and outcome in pediatric acute lymphoblastic leukemia

Mohammad Ali Esmaili; Ahmad Kazemi; Mohammad Faranoush; Hakan Mellstedt; Farhad Zaker; Majid safa; Narjes Mehrvar; Mohammad Reza Rezvany

doi:10.22038/ijbms.2020.41754.9858

Iranian Journal of Basic Medical Sciences (Jun 2020)

Polymorphisms within methotrexate pathway genes: Relationship between plasma methotrexate levels, toxicity experienced and outcome in pediatric acute lymphoblastic leukemia

Mohammad Ali Esmaili,
Ahmad Kazemi,
Mohammad Faranoush,
Hakan Mellstedt,
Farhad Zaker,
Majid safa,
Narjes Mehrvar,
Mohammad Reza Rezvany

Affiliations

Mohammad Ali Esmaili: Department of Hematology, School of Allied Medical Sciences, Iran University of Medical Sciences, Tehran, Iran
Ahmad Kazemi: Department of Hematology, School of Allied Medical Sciences, Iran University of Medical Sciences, Tehran, Iran
Mohammad Faranoush: Pediatric Growth and Development Research Center, Institute of Endocrinology and Metabolism, Iran University of Medical Sciences, Tehran, Iran|Mahak Hematology Oncology Research Center (MAHAK-HORC), Mahak Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran
Hakan Mellstedt: Department of Oncology-Pathology, Immune and Gene Therapy Lab, Cancer Center Karolinska (CCK), Karolinska University Hospital Solna and Karolinska Institute, Stockholm 17176, Sweden
Farhad Zaker: Cellular and Molecular Research Center, School of Allied Medicine, Iran University of Medical Sciences, Tehran, Iran
Majid safa: Cellular and Molecular Research Center, Department of Hematology, Faculty of Allied Medicine, Iran University of Medical Sciences, Tehran, Iran
Narjes Mehrvar: Cancer Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran
Mohammad Reza Rezvany: Department of Hematology, School of Allied Medical Sciences, Iran University of Medical Sciences, Tehran, Iran|Pediatric Growth and Development Research Center, Institute of Endocrinology and Metabolism, Iran University of Medical Sciences, Tehran, Iran|Department of Oncology-Pathology, Immune and Gene Therapy Lab, Cancer Center Karolinska (CCK), Karolinska University Hospital Solna and Karolinska Institute, Stockholm 17176, Sweden

DOI: https://doi.org/10.22038/ijbms.2020.41754.9858
Journal volume & issue: Vol. 23, no. 6
pp. 800 – 809

Abstract

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Objective(s): The current study aimed to investigate the relationship of genetic polymorphism and plasma methotrexate (MTX) levels, toxicity experience and event free survival (EFS) in pediatric acute lymphoblastic leukemia (ALL). Materials and Methods: The study included 74 ALL patients. Polymerase chain reaction and genotyping of methylene tetrahydrofolate reductase (MTHFR) rs1801133, MTHFR rs1801131, ATP-binding cassette superfamily B1 (ABCB1) rs1045642, ATP-binding cassette superfamily G2 (ABCG2) rs2231142 and solute carrier 19A1 (SLC19A1) rs1051266 genetic variations were performed. The plasma MTX levels were investigated at 48 hr after the first dose of MTX infusion.Results: MTHFR rs1801133 TT genotype, ABCBa1 rs1045642 CT genotype and ABCG2 rs2231142 CA genotype revealed a statistically significant association with the MTX plasma levels (PConclusion: Our findings showed that genetic polymorphism could be associated with plasma MTX levels, toxicity experienced and EFS in Iranian pediatric ALL.

Published in Iranian Journal of Basic Medical Sciences

ISSN: 2008-3866 (Print); 2008-3874 (Online)
Publisher: Mashhad University of Medical Sciences
Country of publisher: Iran, Islamic Republic of
LCC subjects: Medicine
Website: http://ijbms.mums.ac.ir/

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