Folate pathway genetic polymorphisms modulate methotrexate-induced toxicity in childhood acute lymphoblastic leukemia

Yousef, Al-Motassem; Farhad, Rand; Alshamaseen, Daniah; Alsheikh, Abrar; Zawiah, Mohammed; Kadi, Taha

doi:10.1007/s00280-019-03776-8

Cited by 18 publications

(25 citation statements)

References 32 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The pharmacodynamic target of MTX is inhibition of DHFR, where the affinity of DHFR for MTX is 1000-fold higher than for folate. However, the GWAS studies [ 49 , 50 , 51 ] and PK studies [ 27 , 43 , 75 ] did not find evidence supporting DHFR polymorphisms to be associated with MTX PK.…”

Section: Resultsmentioning

confidence: 99%

“…MTHFR rs1801133 (C677T–CT or TT genotype) has been associated with increased MTX levels and decreased MTX clearance [ 23 , 26 , 39 , 57 , 71 , 72 , 76 , 78 ]. However, an equal amount of studies have failed to show this association [ 28 , 32 , 34 , 35 , 45 , 46 , 47 , 52 , 73 , 74 , 75 , 77 , 80 ]. In one study, even when there was an association with higher MTX levels, a genetic association of this SNP with renal toxicity could not be established suggesting that other clinical and genetic factors play a role [ 23 ].…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Systematic Review of Pharmacogenetic Factors That Influence High-Dose Methotrexate Pharmacokinetics in Pediatric Malignancies

Taylor

Vang

López-López

et al. 2021

Cancers

View full text Add to dashboard Cite

Methotrexate (MTX) is a mainstay therapeutic agent administered at high doses for the treatment of pediatric and adult malignancies, such as acute lymphoblastic leukemia, osteosarcoma, and lymphoma. Despite the vast evidence for clinical efficacy, high-dose MTX displays significant inter-individual pharmacokinetic variability. Delayed MTX clearance can lead to prolonged, elevated exposure, causing increased risks for nephrotoxicity, mucositis, seizures, and neutropenia. Numerous pharmacogenetic studies have investigated the effects of several genes and polymorphisms on MTX clearance in an attempt to better understand the pharmacokinetic variability and improve patient outcomes. To date, several genes and polymorphisms that affect MTX clearance have been identified. However, evidence for select genes have conflicting results or lack the necessary replication and validation needed to confirm their effects on MTX clearance. Therefore, we performed a systematic review to identify and then summarize the pharmacogenetic factors that influence high-dose MTX pharmacokinetics in pediatric malignancies. Using the PRISMA guidelines, we analyzed 58 articles and 24 different genes that were associated with transporter pharmacology or the folate transport pathway. We conclude that there is only one gene that reliably demonstrates an effect on MTX pharmacokinetics: SLCO1B1.

show abstract

Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Systematic Review of Pharmacogenetic Factors That Influence High-Dose Methotrexate Pharmacokinetics in Pediatric Malignancies

Taylor

Vang

López-López

et al. 2021

Cancers

View full text Add to dashboard Cite

show abstract

“…DHFR and TYMS genes have also been studied in smaller cohorts in relation to hematological toxicity of MTX and to intrinsic resistance to MTX (Yousef et al, 2019). However, these results have also been inconclusive.…”

Section: Genetic Variances and Targetmentioning

confidence: 99%

“…Variants in MTHFR activity have been described and the role of MTHFR polymorphism (mainly C677T and A1298C genotypes) in relation to toxicity has been studied by several groups ( Campbell et al., 2016 ; Ramírez-Pacheco et al., 2016 ; Mahmoud et al., 2018 ; Zhu et al., 2018 ; Yousef et al., 2019 ). However, recent reviews summarized the available data and showed ambiguous results ( Umerez et al., 2017 ; Yao et al., 2019 ), concluding no clear correlation could be established between MTHFR polymorphism and MTX toxicity or relapse data.…”

Section: Role Of Pharmacogenetic Variations In Chemotherapeutic Relatmentioning

confidence: 99%

Pharmacogenomics as a Tool to Limit Acute and Long-Term Adverse Effects of Chemotherapeutics: An Update in Pediatric Oncology

et al. 2020

View full text Add to dashboard Cite

“…The disease is classified into four groups: Acute Myeloid Leukemia (AML); Acute Lymphoblastic Leukemia (ALL); Chronic Myeloid Leukemia (CML), and Chronic Lymphocytic Leukemia (CLL) [5]. ALL constitutes 25% of all types of cancer, representing between 0.5 and 3% of all malignant neoplasms worldwide, being in 2019 the eleventh most common cancer in the world [6]. In ALL, the blasts are homogeneous, the nucleus is regular, the chromatin is homogeneous, small, or nulolytic, with scarce cytoplasm and slight-to-moderate basophilia [7].…”

Section: Introductionmentioning

confidence: 99%

Association between the phenotype of the blood group system AB0 and Leukemia.

et al. 2019

View full text Add to dashboard Cite

The AB0 system has been established as a risk factor or protection associated with the development of multiple pathologies. Thus, the search continues for its association with other diseases. The objective of this study was to determine the association between the AB0 blood system and leukemias. Blood samples were obtained from 102 patients with a presumptive diagnosis of leukemia. We carried out an AB0 typification with Gel-cards. The morphological classification of leukemia was based on the identification of the cellular line and its differentiation stage by means of a peripheral blood smear with Wright staining. The statistical analysis was performed with SAS/STAT® ver. 9.2 statistical software. The X2-Pearson test was utilized for determining the association between two variables. An association was found of AB0 blood groups and leukemias of acute presentation, reporting more cases of those expected for AML in patients with AB blood group and a greater proportion of ALL in those with blood groups A, B, and 0 [X2.-Pearson=102; df=3; p=0.001]. More cases were reported than those expected of CML in patients with blood groups B and CLL than in persons of group 0 [X2-Pearson=6.604; df=1; p=0.017]. According to age group, an association was found of pediatric patients with ALL and adult patients with CLL (X2-Pearson=8.860; df=3; p=0.03). According to the study, the AB0 blood system is associated with leukemias of acute presentation.

show abstract

Folate pathway genetic polymorphisms modulate methotrexate-induced toxicity in childhood acute lymphoblastic leukemia

Cited by 18 publications

References 32 publications

Systematic Review of Pharmacogenetic Factors That Influence High-Dose Methotrexate Pharmacokinetics in Pediatric Malignancies

Systematic Review of Pharmacogenetic Factors That Influence High-Dose Methotrexate Pharmacokinetics in Pediatric Malignancies

Pharmacogenomics as a Tool to Limit Acute and Long-Term Adverse Effects of Chemotherapeutics: An Update in Pediatric Oncology

Association between the phenotype of the blood group system AB0 and Leukemia.

Contact Info

Product

Resources

About