Genetic polymorphisms as predictors of methotrexate toxicity: literature review-Reference-Cited by-同舟云学术

Genetic polymorphisms as predictors of methotrexate toxicity: literature review

Published:2024-04-02 Issue:2 Volume:19 Page:26-33
ISSN:2413-4023
Container-title:Oncohematology
language:
Short-container-title:Onkogematologiâ

Author:

Radzhabova G. A.¹^ORCID,Valiev T. T.²^ORCID,Ryabukhina Yu. E.³^ORCID,Savelyeva M. I.⁴^ORCID,Abdullaev Sh. P.⁵^ORCID,Gurieva O. D.⁶^ORCID,Zeynalova P. A.⁷^ORCID

Affiliation:

1. I.M. Sechenov First Moscow State Medical University, Ministry of Health of Russia (Sechenov University)

2. I.M. Sechenov First Moscow State Medical University, Ministry of Health of Russia (Sechenov University); N.N. Blokhin National Medical Research Center of Oncology, Ministry of Health of Russia

3. Clinical Hospital “Lapino” of the “Mother and Child” Group of companies

4. Yaroslavl State Medical University, Ministry of Health of Russia

5. Russian Medical Academy of Continuing Professional Education, Ministry of Health of Russia

6. N.N. Blokhin National Medical Research Center of Oncology, Ministry of Health of Russia

7. I.M. Sechenov First Moscow State Medical University, Ministry of Health of Russia (Sechenov University); Clinical Hospital “Lapino” of the “Mother and Child” Group of companies

Abstract

Background. A significant advancement in the treatment of high-grade aggressive non-Hodgkin’s lymphomas and acute lymphoblastic leukemia is the inclusion of high-dose (1000–5000 mg/m2) methotrexate in the treatment protocol. This approach has significantly increased the long-term survival rate, but it has been associated with toxicity, requiring supportive care. Factors that predict toxicity were identified, including genes involved in the metabolism (MTHFR) or transport (SLCO1B1) of methotrexate. The analysis of methotrexate metabolism has identified additional genes responsible for the elimination of this drug, allowing for more effective prevention and treatment of methotrexate-associated toxicity.Aim. To study the genetic polymorphisms of enzymes involved in the methotrexate metabolism and associated toxicity in the treatment of pediatric acute lymphoblastic leukemia and non-Hodgkin’s lymphomas.Materials and methods. Data were analyzed in specialized medical databases such as Pubmed, Scopus, Web of Science, Frontiers, and Google Scholar from 2001 to 2024.Results. The main predictors of high-dose methotrexate-associated toxicity are gene polymorphisms in MTHFR, SLCO1B1, ARID5B.Conclusion. Despite the contradictory data presented in the literature, it is important to consider the detection of polymorphisms during high-dose methotrexate treatment in order to administer timely supportive care and prevent significant toxicity.

Publisher

Publishing House ABV Press

Reference57 articles.

1. Rocha J.M., Xavier S.G., de Lima Souza M.E. et al. Current strategies for the detection of minimal residual disease in childhood acute lymphoblastic leukemia. Mediterr J Hematol Infect Dis 2016;8(1):e2016024. DOI: 10.4084/MJHID.2016.024

2. World Health Organization (WHO). International Agency for Research on Cancer 2023. GLOBOCAN 2020: Estimated number of new cases and deaths in 2020, World, both sexes, ages 0–19. Available at: https://gco.iarc.fr.

3. Hunger S.P., Mullighan C.G. Acute lymphoblastic leukemia in children. N Engl J Med 2015;373(16):1541–52. DOI: 10.1056/nejmra1400972

4. Pui C.H., Evans W.E. A 50-year journey to cure childhood acute lymphoblastic leukemia. Semin Hematol 2013;50(3):185–96. DOI: 10.1053/j.seminhematol.2013.06.007

5. Frei E., Freireich E.J., Gehan E. et al. Studies of sequential and combination antimetabolite therapy in acute leukemia: 6-mercaptopurine and methotrexate. Blood 1961;18(4):431–54.