سامانه مدیریت نشریات علمی دانشگاه علوم پزشکی مشهد

Esmaili, Mohammad Ali, Kazemi, Ahmad, Faranoush, Mohammad, Mellstedt, Hakan, Zaker, Farhad, safa, Majid, Mehrvar, Narjes, Rezvany, Mohammad Reza. (1399). Polymorphisms within methotrexate pathway genes: Relationship between plasma methotrexate levels, toxicity experienced and outcome in pediatric acute lymphoblastic leukemia. , 23(6), 800-809. doi: 10.22038/ijbms.2020.41754.9858
Mohammad Ali Esmaili; Ahmad Kazemi; Mohammad Faranoush; Hakan Mellstedt; Farhad Zaker; Majid safa; Narjes Mehrvar; Mohammad Reza Rezvany. "Polymorphisms within methotrexate pathway genes: Relationship between plasma methotrexate levels, toxicity experienced and outcome in pediatric acute lymphoblastic leukemia". , 23, 6, 1399, 800-809. doi: 10.22038/ijbms.2020.41754.9858
Esmaili, Mohammad Ali, Kazemi, Ahmad, Faranoush, Mohammad, Mellstedt, Hakan, Zaker, Farhad, safa, Majid, Mehrvar, Narjes, Rezvany, Mohammad Reza. (1399). 'Polymorphisms within methotrexate pathway genes: Relationship between plasma methotrexate levels, toxicity experienced and outcome in pediatric acute lymphoblastic leukemia', , 23(6), pp. 800-809. doi: 10.22038/ijbms.2020.41754.9858
Esmaili, Mohammad Ali, Kazemi, Ahmad, Faranoush, Mohammad, Mellstedt, Hakan, Zaker, Farhad, safa, Majid, Mehrvar, Narjes, Rezvany, Mohammad Reza. Polymorphisms within methotrexate pathway genes: Relationship between plasma methotrexate levels, toxicity experienced and outcome in pediatric acute lymphoblastic leukemia. , 1399; 23(6): 800-809. doi: 10.22038/ijbms.2020.41754.9858

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

Iranian Journal of Basic Medical Sciences
مقاله 13، دوره 23، شماره 6، شهریور 2020، صفحه 800-809    اصل مقاله (673.14 K)
نوع مقاله: Original Article
شناسه دیجیتال (DOI): 10.22038/ijbms.2020.41754.9858
نویسندگان
Mohammad Ali Esmaili1؛ Ahmad Kazemi1؛ Mohammad Faranoush2، 3؛ Hakan Mellstedt4؛ Farhad Zaker5؛ Majid safa6؛ Narjes Mehrvar7؛ Mohammad Reza Rezvany* 1، 2، 4
1Department of Hematology, School of Allied Medical Sciences, Iran University of Medical Sciences, Tehran, Iran
2Pediatric Growth and Development Research Center, Institute of Endocrinology and Metabolism, Iran University of Medical Sciences, Tehran, Iran
3Mahak Hematology Oncology Research Center (MAHAK-HORC), Mahak Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran
4Department of Oncology-Pathology, Immune and Gene Therapy Lab, Cancer Center Karolinska (CCK), Karolinska University Hospital Solna and Karolinska Institute, Stockholm 17176, Sweden
5Cellular and Molecular Research Center, School of Allied Medicine, Iran University of Medical Sciences, Tehran, Iran
6Cellular and Molecular Research Center, Department of Hematology, Faculty of Allied Medicine, Iran University of Medical Sciences, Tehran, Iran
7Cancer Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran
چکیده
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 (P<0.01, P<0.05, P<0.05, respectively). The MTHFR rs1801133 TT genotype had a statistically significant association with hematopoietic toxicity (P<0.01) and interventions (P<0.05). The MTHFR rs1801131 AC genotype was related to the decreased hepatic toxicity (P<0.05). The SLC19A1 rs 1051266 GA genotype was related to the increased hepatic toxicity (P<0.05). Only the ABCB1 rs1045642 CT and TT genotypes had a statistically significant correlation with EFS (P<0.05, P<0.05, respectively).   
Conclusion: Our findings showed that genetic polymorphism could be associated with plasma MTX levels, toxicity experienced and EFS in Iranian pediatric ALL.   
کلیدواژه‌ها
ABCB1؛ ABCG2؛ Genetic polymorphism؛ Genotype؛ Methotrexate؛ MTHFR؛ Pediatric acute lymphoblastic- leukemia؛ SLC19A1
مراجع
1. Kodidela S, Suresh Chandra P, Dubashi B. Pharmacogenetics of methotrexate in acute lymphoblastic leukaemia: why still at the bench level? Eur J Clin Pharmacol 2014; 70:253-260.
2. Olarte Carrillo I, Ramos Penafiel C, Miranda Peralta E, Rozen Fuller E, Kassack Ipina JJ, Centeno Cruz F, et al. Clinical significance of the ABCB1 and ABCG2 gene expression levels in acute lymphoblastic leukemia. Hematology 2017; 22:286-291.
3. Wojtuszkiewicz A, Peters GJ, van Woerden NL, Dubbelman B, Escherich G, Schmiegelow K, et al. Methotrexate resistance in relation to treatment outcome in childhood acute lymphoblastic leukemia. J Hematol Oncol 2015; 8:61.
4. Howard SC, McCormick J, Pui CH, Buddington RK, Harvey RD. Preventing and Managing Toxicities of High-Dose Methotrexate. Oncologist 2016; 21:1471-1482.
5. Ranchon F, Vantard N, Henin E, Bachy E, Sarkozy C, Karlin L, et al. Delayed methotrexate elimination: Incidence, interaction with antacid drugs, and clinical consequences? Hematol Oncol 2018; 36:399-406.
6. Sharifi MJ, Bahoush G, Zaker F, Ansari S, Rafsanjani KA, Sharafi HJPh, et al. Association of-24CT, 1249GA, and 3972CT ABCC2 gene polymorphisms with methotrexate serum levels and toxic side effects in children with acute lymphoblastic leukemia.  2014; 31:169-177.
7. Kalantari A, Zaker F, Ansari S, Sharafi H, Mohammadian MJTR. The effect of polymorphisms of gamma-glutamyl hydrolase (GGH) gene on methotrexate-induced toxicity in acute lymphoblastic leukemia.  2015; 34:136-141.
8. Suthandiram S, Gan GG, Zain SM, Bee PC, Lian LH, Chang KM, et al. Effect of polymorphisms within methotrexate pathway genes on methotrexate toxicity and plasma levels in adults with hematological malignancies. Pharmacogenomics 2014; 15:1479-1494.
9. Mahmoud LB, Mdhaffar M, Frikha R, Ghozzi H, Hakim A, Sahnoun Z, et al. Use of MTHFR C677T polymorphism and plasma pharmacokinetics to predict methotrexate toxicity in patients with acute lymphoblastic leukemia. Adv Clin Exp Med 2018; 27:1061-1068.
10. Giletti A, Esperon P. Genetic markers in methotrexate treatments. Pharmacogenomics J 2018; 18:689-703.
11. Chiusolo P, Giammarco S, Bellesi S, Metafuni E, Piccirillo N, De Ritis D, et al. The role of MTHFR and RFC1 polymorphisms on toxicity and outcome of adult patients with hematological malignancies treated with high-dose methotrexate followed by leucovorin rescue. Cancer chemotherapy and pharmacology 2012; 69:691-696.
12. Radtke S, Zolk O, Renner B, Paulides M, Zimmermann M, Moricke A, et al. Germline genetic variations in methotrexate candidate genes are associated with pharmacokinetics, toxicity, and outcome in childhood acute lymphoblastic leukemia. Blood 2013; 121:5145-5153.
13. Avivi I, Zuckerman T, Krivoy N, Efrati E. Genetic polymorphisms predicting methotrexate blood levels and toxicity in adult non-Hodgkin lymphoma. Leuk Lymphoma 2014; 55:565-570.
14. Yazıcıoğlu B, Kaya Z, Ergun SG, Perçin F, Koçak Ü, Yenicesu İ, et al. Influence of folate-related gene polymorphisms on high-dose methotrexate-related toxicity and prognosis in Turkish children with acute lymphoblastic leukemia. Turk J Haematol 2017; 34:143-150.
15. Liu SG, Li ZG, Cui L, Gao C, Li WJ, Zhao XX. Effects of methylenetetrahydrofolate reductase gene polymorphisms on toxicities during consolidation therapy in pediatric acute lymphoblastic leukemia in a Chinese population. Leuk Lymphoma 2011; 52:1030-1040.
16. Perez C, Wang YM, Sutow WW, Herson J. Significance of the 48-hour plasma level in high-dose methotrexate regimens. Cancer Clin Trials 1978; 1:107-111.
17. Trotti A, Colevas AD, Setser A, Rusch V, Jaques D, Budach V, et al. CTCAE v3.0: development of a comprehensive grading system for the adverse effects of cancer treatment. Semin Radiat Oncol 2003; 13:176-181.
18. Liu SG, Gao C, Zhang RD, Zhao XX, Cui L, Li WJ, et al. Polymorphisms in methotrexate transporters and their relationship to plasma methotrexate levels, toxicity of high-dose methotrexate, and outcome of pediatric acute lymphoblastic leukemia. Oncotarget 2017; 8:37761-37772.
19. Sepe DM, McWilliams T, Chen J, Kershenbaum A, Zhao H, La M, et al. Germline genetic variation and treatment response on CCG-1891. Pediatr Blood Cancer 2012; 58:695-700.
20. Imanishi H, Okamura N, Yagi M, Noro Y, Moriya Y, Nakamura T, et al. Genetic polymorphisms associated with adverse events and elimination of methotrexate in childhood acute lymphoblastic leukemia and malignant lymphoma. J Hum Genet 2007; 52:166-171.
21. Kantar M, Kosova B, Cetingul N, Gumus S, Toroslu E, Zafer N, et al. Methylenetetrahydrofolate reductase C677T and A1298C gene polymorphisms and therapy-related toxicity in children treated for acute lymphoblastic leukemia and non-Hodgkin lymphoma. Leuk Lymphoma 2009; 50:912-917.
22. Tantawy AA, El-Bostany EA, Adly AA, Abou El Asrar M, El-Ghouroury EA, Abdulghaffar EE. Methylene tetrahydrofolate reductase gene polymorphism in Egyptian children with acute lymphoblastic leukemia. Blood Coagul Fibrinolysis 2010; 21:28-34.
23. Salazar J, Altes A, Del Rio E, Estella J, Rives S, Tasso M, et al. Methotrexate consolidation treatment according to pharmacogenetics of MTHFR ameliorates event-free survival in childhood acute lymphoblastic leukaemia.  Pharmacogenomics J 2012; 12:379-385.
24. Liu J, Chen J, Tan W, Lin D. Association between MTHFR gene polymorphisms and toxicity of HDMTX chemotherapy in acute lymphocytic leukemia. Zhongguo Shi Yan Xue Ye Xue Za Zhi 2008; 16:488-492.
25. Lazić J, Kotur N, Krstovski N, Dokmanović L, Zukić B, Predojević-Samardžić J, et al. Importance of pharmacogenetic markers in the methylenetetrahydrofolate reductase gene during methotrexate treatment in pediatric patients with acute lymphoblastic leukemia.  Arch Biol Sci 2017; 69:239-246.
26. van Kooten Niekerk PB, Schmiegelow K, Schroeder H. Influence of methylene tetrahydrofolate reductase polymorphisms and coadministration of antimetabolites on toxicity after high dose methotrexate. Eur J Haematol 2008; 81:391-398.
27. Erčulj N, Kotnik BF, Debeljak M, Jazbec J, Dolžan V. Influence of folate pathway polymorphisms on high-dose methotrexate-related toxicity and survival in childhood acute lymphoblastic leukemia. Leuk Lymphoma 2012; 53:1096-1104.
28. Karathanasis NV, Stiakaki E, Goulielmos GN, Kalmanti M. The role of the methylenetetrahydrofolate reductase 677 and 1298 polymorphisms in Cretan children with acute lymphoblastic leukemia. Genet Test Mol Biomarkers 2011; 15:5-10.
29. Aplenc R, Thompson J, Han P, La M, Zhao H, Lange B, et al. Methylenetetrahydrofolate reductase polymorphisms and therapy response in pediatric acute lymphoblastic leukemia. Cancer Res 2005; 65:2482-2487.
30. D’Angelo V, Ramaglia M, Iannotta A, Crisci S, Indolfi P, Francese M, et al. Methotrexate toxicity and efficacy during the consolidation phase in paediatric acute lymphoblastic leukaemia and MTHFR polymorphisms as pharmacogenetic determinants. Cancer Chemother Pharmacol 2011; 68:1339-1346.
31. Huang L, Tissing WJ, de Jonge R, van Zelst BD, Pieters R. Polymorphisms in folate-related genes: association with side effects of high-dose methotrexate in childhood acute lymphoblastic leukemia. Leukemia 2008; 22:1798-1800.
32. Zaker F, Ansari S, Toosi B, Sayadi M, Sharafi HJJDD. The relationship of Polymorphism of RFC-I Gene on Methotrexate Serum Level and Related Toxicity in Pediatric Acute Lymphoblastic Leukemia.  J Dev Drugs 2017; 6:2.
33. Eissa DS, Ahmed TM. C677T and A1298C polymorphisms of the methylenetetrahydrofolate reductase gene: effect on methotrexate-related toxicity in adult acute lymphoblastic leukaemia. Blood Coagul Fibrinolysis 2013; 24:181-188.
34. Zhu C, Liu YW, Wang SZ, Li XL, Nie XL, Yu XT, et al. Associations between the C677T and A1298C polymorphisms of MTHFR and the toxicity of methotrexate in childhood malignancies: a meta-analysis. Pharmacogenomics J 2018; 18:450-459.
35. Yang L, Hu X, Xu L. Impact of methylenetetrahydrofolate reductase (MTHFR) polymorphisms on methotrexate-induced toxicities in acute lymphoblastic leukemia: a meta-analysis. Tumour Biol 2012; 33:1445-1454.
36. Song GG, Bae SC, Lee YH. Association of the MTHFR C677T and A1298C polymorphisms with methotrexate toxicity in rheumatoid arthritis: a meta-analysis. Clin Rheumatol 2014; 33:1715-1724.
37. Goyal RK. MTHFR 677 C> T genotype and adverse outcomes in treatment of childhood ALL: Is the jury in? Pediatric blood & cancer 2009; 52:316-317.
38. Chiusolo P, Reddiconto G, Farina G, Mannocci A, Fiorini A, Palladino M, et al. MTHFR polymorphisms’ influence on outcome and toxicity in acute lymphoblastic leukemia patients. Leukemia research 2007; 31:1669-1674.
39. El-Khodary NM, El-Haggar SM, Eid MA, Ebeid EN. Study of the pharmacokinetic and pharmacogenetic contribution to the toxicity of high-dose methotrexate in children with acute lymphoblastic leukemia. Med Oncol 2012; 29:2053-2062.
40. Zhao M, Liang L, Ji L, Chen D, Zhang Y, Zhu Y, et al. MTHFR gene polymorphisms and methotrexate toxicity in adult patients with hematological malignancies: a meta-analysis. Pharmacogenomics 2016; 17:1005-1017.
41. Spyridopoulou KP, Dimou NL, Hamodrakas SJ, Bagos PG. Methylene tetrahydrofolate reductase gene polymorphisms and their association with methotrexate toxicity: a meta-analysis. Pharmacogenet Genomics 2012; 22:117-133.
42. Lopez-Lopez E, Martin-Guerrero I, Ballesteros J, Garcia-Orad A. A systematic review and meta-analysis of MTHFR polymorphisms in methotrexate toxicity prediction in pediatric acute lymphoblastic leukemia. Pharmacogenomics J 2013; 13:498-506.
43. Yao P, He X, Zhang R, Tong R, Xiao H. The influence of MTHFR genetic polymorphisms on adverse reactions after methotrexate in patients with hematological malignancies: a meta-analysis. Hematology 2019; 24:10-19.
44. He HR, Liu P, He GH, Dong WH, Wang MY, Dong YL, et al. Association between reduced folate carrier G80A polymorphism and methotrexate toxicity in childhood acute lymphoblastic leukemia: a meta-analysis. Leuk Lymphoma 2014; 55:2793-2800.
45. Ojha RP, Gurney JG. Methylenetetrahydrofolate reductase C677T and overall survival in pediatric acute lymphoblastic leukemia: a systematic review.  Leuk Lymphoma 2014; 55:67-73.

آمار
تعداد مشاهده مقاله: 1,337
تعداد دریافت فایل اصل مقاله: 720