The Effects of Three ABCG2 Polymorphisms on Outcome of Central Nervous System Relapses in Iranian Children With Acute Lymphoblastic Leukemia Receiving High Dose Methotrexate
-
Raziye Karamikhah
,
Negar Azarpira
,
Soheila Zareifar
,
Ali Dehshari
,
Soha Namazi
,
Mohammad Hossein Anbardar
,
Iman Karimzade
Abstract
- Methotrexate (MTX) is the main drug for the treatment of childhood acute lymphoblastic leukemia (ALL). ABCG2 pump is the main transporter of MTX on BBB. Our aim was to investigate the possible relationship between three polymorphisms of the ABCG2 gene, and isolated CNS relapses in Iranian children with ALL receiving high dose MTX. Genotyping of three polymorphisms of the ABCG2 gene, including G34A, C376T, and C421A, was performed by the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method for 56 patients. A high frequency of C376T CT genotype was observed among the patients. There was no significant association between C376T and C421 and isolated CNS relapse (P>0.05). C376T and C421A polymorphisms are not associated with isolated CNS relapse in childhood ALL.
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2. Plasschaert S, van der Kolk D, de Bont E, Kamps W, Morisaki K, Bates S, et al. The role of breast cancer resistance protein in acute lymphoblastic leukemia. Clin Cancer Res 2003;9:5171-7.
3. Eyal S, Hsiao P, Unadkat J. Drug interactions at the blood-brain barrier. Fact or fantasy? Pharmacol ther 2009;123:80-104.
4. Vasiliou V, Vasiliou K, Nebert D. Human ATP-binding cassette (ABC) transporter family. Hum Genomics 2009;3:281-90.
5. Natarajan K, Xie Y, Baer M, Ross D. Role of breast cancer resistance protein (BCRP/ABCG2) in cancer drug resistance. Biochem Pharmacol 2012;83:1084-103.
6. Couraud PO, Sandrine S. Blood- brain barrier models for investigating CNS pathologies. In: Pasquanlini R, Wadih A, eds. Protein Discovery Technologies. United States: CRC Press, 2009:62.
7. Kobayashi D, Ieiri I, Hirota T, Takane H, Maegawa S, Kigawa J. Functional assessment of ABCG2 (BCRP) gene polymorphisms to protein expression in human placenta. Drug Metab Dispos 2005;33:94-101.
8. El Mesallamy HOE, Rashed WM, Hamdy NM, Hamdy N. High-dose methotrexate in Egyptian pediatric acute lymphoblastic leukemia: the impact of ABCG2 C421A genetic polymorphism on plasma levels, what is next? J Cancer Res Clin Oncol 2014;140:1359-65.
9. Imai Y, Nakane M, Kage K, Tsukahara S, Ishikawa E, Tsuruo T. C421A polymorphism in the human breast cancer resistance protein gene is associated with low expression of Q141K protein and low- drug resistance. Mol Cancer Ther 2002;1:611-6.
10. Mimeto H, Kato R, Ito A, Kasamatsu S, Ikegami Y, Kii I. A functional study on polymorphism of the ATP-binding cassette transporter ABCG2: critical role of arginine-482 in methotrexate transport. Biochem J 2003;373:767-74.
11. Sharifi M, Bahoush G, Zaker F, Ansari S, Arjmandi Rafsanjani K, Sharafi H. Association of -24CT, 1249GA, and 3972CT ABCC2 gene polymorphisms with methotrexate serum levels and toxic side effects in children with acute lymphoblastic leukemia. Pedit Hematol Onc 2014;31:169-77.
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13. Packer RJ, Schiff D. Neuro-oncology. Chichester, West Sussex: Chichester, West Sussex:Wiley-Blackwell, 2012.
14. You G, Morris M. Drug transporters: molecular characterization & role in drug disposition. Hoboken, NJ: Wiley-interscience, 2007.
15. Lanzkowsky P, Lipton JM, Fish JD. Lanskowsky's manual of pediatric hematology and oncology. 6th ed. Amsterdam: Elsevier Science, 2016.
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17. Niebudek K, Balcerczak E, Mirowski M, Pietrrzak J, Zawadzka I, Nawrocka MZ. The contribution of ABCG2 G34A and C421A polymorphisms to multiple myeloma susceptility. Onco Targets and Therapy 2019;12:1655-60.
18. Kim HS, Sunwoo YE, Ryu JY, Kang HJ, Jung HE, Song IS, et al. The effect of ABCG2 V12M, Q141K and Q126X, known functional variants in vitro, on the disposition of lamivudine. Br J Clin Pharmacol 2007;64:645-54.
19. Mehrvar N, Rezvany MR, Abolghasemi H, Akbari ME, SaberyNejad J, Mehrvar A, et al. Gene expression of ABCG1, ABCG2, and ABCB1 and their role in Iranian pediatric pateints with acute lymphoblastic leukemia's recurrence. Int J Cancer Manag 2019;12:e93300.
20. Sane R, Wu SP, Zhang R, Gallo JM. The effect of ABCG2 and ABCC4 on the pharmacokinetics of methotrexate in the brain. Drug Metab Dispos 2014;42:537-40.
21. Borsi JD, Moe PJ. Systemic clearance of methotrexate in the prognosis of acute lymphoblastic leukemia in children. Cancer 1987;60:3020-4.
22. Rodman JH, Sunderland M, Kavanagh RL, Ochs J, Yalowich J, Evans WE, et al. Pharmacokinetcs of continuous infusion of methotrexate and teniposide in pediatric cancer patients. Cancer Res 1990;50:4267-71.
23. Stanulla M, Schaeffeler E, Arens S, Rathmann A, Schrauder A, Welte K, et al. GSTP1 and MDR1 genotypes and central nervous system relapse in childhood acute lymphoblastic leukemia. Int J Hematol 2005;81:39-44.
24. Stanulla M, Schrauder A, Welte K, Schrappe M. Tumor necrosis factor and lymphotoxin-alpha genetic polymorphisms and risk of relapse in childhood B-cell precursor acute lymphoblastic leukemia: a case-control study of patients treated with BFM. BMC Blood Disord 2001;1:2.
25. Rocha JCC, Cheng C, Liu W, Kishi S, Das S, Cook EH, et al. Pharmacogenetics of outcome in children with acute lymphoblastic leukemia. Blood 2005;105:4752-8.
26. Ansari M, Sauty G, Labuda M, VGagne' V, JRousseau J, Moghrabi A, et al. polymorphism in multidrug resistance-associated protein gene 3 is associated with outcomes in childhood acute lymphoblastic leukemia. Pharmacogenomics J 2012;12:386-94.
27. Zhai X, Wang H, Zhu X, Miao H, Qian X, Li J, et al. Gene polymorphisms of ABC transporters are associated with clinical outcomes in children with acute lymphoblastic leukemia. Arch Med Sci 2012;8:659-71.
28. Semsei AF, Erdélyi DJ, Ungvári I, Kámory E, Csókay B, Andrikovics H, et al. Association of some rare haplotypes and genotype combinations in the MDR1 gene with childhood acute lymphoblastic leukaemia. Leuk Res 2008;32:1214-20.
29. Imanishi H, Okamura N, Yagi MN, Moriya Y, Nakamura T, Hayakawa A, et al. Genetic polymorphisms associated with adverse events and elimination of methotrexate in childhood acute lymphoblastic leukemia and malignant lymphoma. J Hum Genet 2007;52:166-71.
30. Lopez-Lopez E, Martin-Guerrero I, Ballesteros J, Piñan MA, Garcia-Miguel P, Navajas A, et al. Polymorphisms of the SLCO1B1 gene predict methotrexate-related toxicity in childhood acute lymphoblastic leukemia. Pediatr Blood Cancer 2011;57:612-9.
31. 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;15:1479-94.
32. Gervasini G, de Murillo SG, Jiménez M, de la Maya MD, Vagace JM. Effect of polymorphisms in transporter genes on dosing, efficacy and toxicity of maintenance therapy in children with acute lymphoblastic leukemia. Gene 2017;628:72-7.
33. 33. Horinouchi M, Yagi M, Imanishi H, Mori T, Yanai T, Hayakawa A, et al. ssociation of genetic polymorphisms with hepatotoxicity in patients with childhood acute lymphoblastic leukemia or lymphoma. Pediatr Hematol Oncol 2010;27:344-54.
34. Yang L, Liu L, Wang J, Qiu L, Mi Y, Ma X, et al. Polymorphisms in folate-related genes: impact on risk of adult acute lymphoblastic leukemia rather than pediatric in Han Chinese. Leuk Lymphoma 2011;52:1770-6.
35. Mc Lead LH, Evans WE. Clinical pharmacodynamics of anticancer drugs. In: Derendorf H, Guenther H, eds. Handbook of pharmacokinetic/pharmacodynamic correlation. Boca Raton, Florida: CRC Press LLC, 1995:398.
36. Erdilyi DJ, Kámory E, Csókay B, Andrikovics H, Tordai A, Kiss C, et al. Synergistic interaction of ABCB1 and ABCG2 polymorphisms predicts the prevalence of toxic encephalopathy during anticancer chemotherapy. Pharmacogenomics J 2008;8:321-7.
2. Plasschaert S, van der Kolk D, de Bont E, Kamps W, Morisaki K, Bates S, et al. The role of breast cancer resistance protein in acute lymphoblastic leukemia. Clin Cancer Res 2003;9:5171-7.
3. Eyal S, Hsiao P, Unadkat J. Drug interactions at the blood-brain barrier. Fact or fantasy? Pharmacol ther 2009;123:80-104.
4. Vasiliou V, Vasiliou K, Nebert D. Human ATP-binding cassette (ABC) transporter family. Hum Genomics 2009;3:281-90.
5. Natarajan K, Xie Y, Baer M, Ross D. Role of breast cancer resistance protein (BCRP/ABCG2) in cancer drug resistance. Biochem Pharmacol 2012;83:1084-103.
6. Couraud PO, Sandrine S. Blood- brain barrier models for investigating CNS pathologies. In: Pasquanlini R, Wadih A, eds. Protein Discovery Technologies. United States: CRC Press, 2009:62.
7. Kobayashi D, Ieiri I, Hirota T, Takane H, Maegawa S, Kigawa J. Functional assessment of ABCG2 (BCRP) gene polymorphisms to protein expression in human placenta. Drug Metab Dispos 2005;33:94-101.
8. El Mesallamy HOE, Rashed WM, Hamdy NM, Hamdy N. High-dose methotrexate in Egyptian pediatric acute lymphoblastic leukemia: the impact of ABCG2 C421A genetic polymorphism on plasma levels, what is next? J Cancer Res Clin Oncol 2014;140:1359-65.
9. Imai Y, Nakane M, Kage K, Tsukahara S, Ishikawa E, Tsuruo T. C421A polymorphism in the human breast cancer resistance protein gene is associated with low expression of Q141K protein and low- drug resistance. Mol Cancer Ther 2002;1:611-6.
10. Mimeto H, Kato R, Ito A, Kasamatsu S, Ikegami Y, Kii I. A functional study on polymorphism of the ATP-binding cassette transporter ABCG2: critical role of arginine-482 in methotrexate transport. Biochem J 2003;373:767-74.
11. Sharifi M, Bahoush G, Zaker F, Ansari S, Arjmandi Rafsanjani K, Sharafi H. Association of -24CT, 1249GA, and 3972CT ABCC2 gene polymorphisms with methotrexate serum levels and toxic side effects in children with acute lymphoblastic leukemia. Pedit Hematol Onc 2014;31:169-77.
12. Niemann A, Muhlisch J, Fruhwald M, Gerß J, Hempel G, Boos J. Therapeutic Drug Monitoring of Methotrexate in Cerebrospinal Fluid After Systemic High-Dose Infusion in Children: Can the Burden of Intrathecal Methotrexate be Reduced? Ther Drug Monit 2010;32:467-75.
13. Packer RJ, Schiff D. Neuro-oncology. Chichester, West Sussex: Chichester, West Sussex:Wiley-Blackwell, 2012.
14. You G, Morris M. Drug transporters: molecular characterization & role in drug disposition. Hoboken, NJ: Wiley-interscience, 2007.
15. Lanzkowsky P, Lipton JM, Fish JD. Lanskowsky's manual of pediatric hematology and oncology. 6th ed. Amsterdam: Elsevier Science, 2016.
16. Heyes N, Kapoor P, Kerr ID. Polymorphisms of the multidrug pump ABCG2: a systematic review of their effect on protein expression, function and drug pharmacokineticd. Drug Metab Dispos 2018;46:1886-99.
17. Niebudek K, Balcerczak E, Mirowski M, Pietrrzak J, Zawadzka I, Nawrocka MZ. The contribution of ABCG2 G34A and C421A polymorphisms to multiple myeloma susceptility. Onco Targets and Therapy 2019;12:1655-60.
18. Kim HS, Sunwoo YE, Ryu JY, Kang HJ, Jung HE, Song IS, et al. The effect of ABCG2 V12M, Q141K and Q126X, known functional variants in vitro, on the disposition of lamivudine. Br J Clin Pharmacol 2007;64:645-54.
19. Mehrvar N, Rezvany MR, Abolghasemi H, Akbari ME, SaberyNejad J, Mehrvar A, et al. Gene expression of ABCG1, ABCG2, and ABCB1 and their role in Iranian pediatric pateints with acute lymphoblastic leukemia's recurrence. Int J Cancer Manag 2019;12:e93300.
20. Sane R, Wu SP, Zhang R, Gallo JM. The effect of ABCG2 and ABCC4 on the pharmacokinetics of methotrexate in the brain. Drug Metab Dispos 2014;42:537-40.
21. Borsi JD, Moe PJ. Systemic clearance of methotrexate in the prognosis of acute lymphoblastic leukemia in children. Cancer 1987;60:3020-4.
22. Rodman JH, Sunderland M, Kavanagh RL, Ochs J, Yalowich J, Evans WE, et al. Pharmacokinetcs of continuous infusion of methotrexate and teniposide in pediatric cancer patients. Cancer Res 1990;50:4267-71.
23. Stanulla M, Schaeffeler E, Arens S, Rathmann A, Schrauder A, Welte K, et al. GSTP1 and MDR1 genotypes and central nervous system relapse in childhood acute lymphoblastic leukemia. Int J Hematol 2005;81:39-44.
24. Stanulla M, Schrauder A, Welte K, Schrappe M. Tumor necrosis factor and lymphotoxin-alpha genetic polymorphisms and risk of relapse in childhood B-cell precursor acute lymphoblastic leukemia: a case-control study of patients treated with BFM. BMC Blood Disord 2001;1:2.
25. Rocha JCC, Cheng C, Liu W, Kishi S, Das S, Cook EH, et al. Pharmacogenetics of outcome in children with acute lymphoblastic leukemia. Blood 2005;105:4752-8.
26. Ansari M, Sauty G, Labuda M, VGagne' V, JRousseau J, Moghrabi A, et al. polymorphism in multidrug resistance-associated protein gene 3 is associated with outcomes in childhood acute lymphoblastic leukemia. Pharmacogenomics J 2012;12:386-94.
27. Zhai X, Wang H, Zhu X, Miao H, Qian X, Li J, et al. Gene polymorphisms of ABC transporters are associated with clinical outcomes in children with acute lymphoblastic leukemia. Arch Med Sci 2012;8:659-71.
28. Semsei AF, Erdélyi DJ, Ungvári I, Kámory E, Csókay B, Andrikovics H, et al. Association of some rare haplotypes and genotype combinations in the MDR1 gene with childhood acute lymphoblastic leukaemia. Leuk Res 2008;32:1214-20.
29. Imanishi H, Okamura N, Yagi MN, Moriya Y, Nakamura T, Hayakawa A, et al. Genetic polymorphisms associated with adverse events and elimination of methotrexate in childhood acute lymphoblastic leukemia and malignant lymphoma. J Hum Genet 2007;52:166-71.
30. Lopez-Lopez E, Martin-Guerrero I, Ballesteros J, Piñan MA, Garcia-Miguel P, Navajas A, et al. Polymorphisms of the SLCO1B1 gene predict methotrexate-related toxicity in childhood acute lymphoblastic leukemia. Pediatr Blood Cancer 2011;57:612-9.
31. 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;15:1479-94.
32. Gervasini G, de Murillo SG, Jiménez M, de la Maya MD, Vagace JM. Effect of polymorphisms in transporter genes on dosing, efficacy and toxicity of maintenance therapy in children with acute lymphoblastic leukemia. Gene 2017;628:72-7.
33. 33. Horinouchi M, Yagi M, Imanishi H, Mori T, Yanai T, Hayakawa A, et al. ssociation of genetic polymorphisms with hepatotoxicity in patients with childhood acute lymphoblastic leukemia or lymphoma. Pediatr Hematol Oncol 2010;27:344-54.
34. Yang L, Liu L, Wang J, Qiu L, Mi Y, Ma X, et al. Polymorphisms in folate-related genes: impact on risk of adult acute lymphoblastic leukemia rather than pediatric in Han Chinese. Leuk Lymphoma 2011;52:1770-6.
35. Mc Lead LH, Evans WE. Clinical pharmacodynamics of anticancer drugs. In: Derendorf H, Guenther H, eds. Handbook of pharmacokinetic/pharmacodynamic correlation. Boca Raton, Florida: CRC Press LLC, 1995:398.
36. Erdilyi DJ, Kámory E, Csókay B, Andrikovics H, Tordai A, Kiss C, et al. Synergistic interaction of ABCB1 and ABCG2 polymorphisms predicts the prevalence of toxic encephalopathy during anticancer chemotherapy. Pharmacogenomics J 2008;8:321-7.
| Files | ||
| Issue | Vol 59, No 3 (2021) | |
| Section | Articles | |
| DOI | https://doi.org/10.18502/acta.v59i3.5783 | |
| Keywords | ||
| Methotrexate ATP-binding cassette transporter G2 (ABCG2) Central nervous system (CNS) relapse Childhood acute lymphoblastic leukemia | ||
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How to Cite
1.
Karamikhah R, Azarpira N, Zareifar S, Dehshari A, Namazi S, Anbardar MH, Karimzade I. The Effects of Three ABCG2 Polymorphisms on Outcome of Central Nervous System Relapses in Iranian Children With Acute Lymphoblastic Leukemia Receiving High Dose Methotrexate. Acta Med Iran. 2021;59(3):133-141.
