Evaluating Methotrexate Toxicity and Its Association with ABCB1 Genetic Polymorphism in Children with Acute Lymphoblastic Leukemia
| Author | Farima Zakaryaei | en |
| Author | Ebrahim Mohammadi | en |
| Author | Ebrahim Ghaderi | en |
| Author | Fatemeh Zamani | en |
| Author | Borhan Moradveisi | en |
| Orcid | Farima Zakaryaei [0000-0003-0114-0788] | en |
| Orcid | Ebrahim Ghaderi [0000-0002-2303-1657] | en |
| Orcid | Borhan Moradveisi [0000-0002-1952-4344] | en |
| Issued Date | 2022-02-28 | en |
| Abstract | Background: Acute lymphoblastic leukemia (ALL) is among the most prevalent type of hematologic malignancy in children. The Children’s Oncology Group protocol recognizes methotrexate (MTX) as a therapy for this problem in children, despite its several complications. The relationship between MTX toxicity and ATP-binding cassette subfamily B member 1 (ABCB1) SNPs in ALL children patients has been investigated in many studies. Objectives: Regarding the controversial findings reported by these studies, the present work aims to evaluate Methotrexate toxicity and its association with ABCB1 Genetic Polymorphism in ALL pediatric patients. Methods: Blood samples were collected from pediatric ALL patients. Next, DNA was extracted and polymerase chain reaction (PCR) was conducted using 300 μMol/μL of direct primers in 50 µL as the ultimate volume. ABCB1 gene was amplified using the PCR technique, and 0.5% agarose gel electrophoresis was used to identify reaction products. Afterward, the PCR fragments’ length was proved by observing through UV-transilluminator. Finally, liver and blood toxicity was studied in all cases under treatment with MTX. Results: In the present study, 81 children with ALL (36 females and 45 males) with a mean age of 6.32 ± 3.08 years old were examined. The ABCB1 1199 G->A gene mutation frequency and the ABCB1 3435 C->T gene mutation frequency was 4.9 and 70.4%, respectively. The results showed no statistically significant difference between leukopenia, gastrointestinal toxicity, renal toxicity, hepatotoxicity, anemia, thrombocytopenia, and neutropenia in cases having homozygous heterozygous ABCB1 3435 C->T and ABCB1 1199 G->A mutant polymorphisms than those having ordinary polymorphism. Conclusions: Overall, it seems that C3435 T, G1199A, and ABCB1 are not significant MTX toxicity markers in pediatric ALL cases. | en |
| DOI | https://doi.org/10.5812/ijp.115502 | en |
| Keyword | Methotrexate | en |
| Keyword | Acute Lymphoblastic Leukemia | en |
| Keyword | ABCB1 Gene | en |
| Keyword | Drug Complications | en |
| Publisher | Brieflands | en |
| Title | Evaluating Methotrexate Toxicity and Its Association with ABCB1 Genetic Polymorphism in Children with Acute Lymphoblastic Leukemia | en |
| Type | Research Article | en |