Mexican Childhood Acute Lymphoblastic Leukemia: A Pilot Study of the MDR1 and MTHFR Gene Polymorphisms and Their Associations with Clinical Outcomes

Abstract

MDR1 rs1045642 and MTHFR rs1801133 should be considered as diagnostic candidates for the identification of pediatric patients with a high risk of suffering adverse events during ALL treatment.

Clinical relevance of multi-drug resistance gene C3435T polymorphism in diffuse large B-cell lymphoma in Xinjiang

“…A Mexican study [ 21 , 22 ] showed that children with acute lymphoblastic leukemia carrying CC genotype had a reduced risk of leukopenia, while another study showed that children with acute lymphoblastic leukemia carrying TT genotype had an increased risk of myelosuppression after chemotherapy, which was not observed in our study though. It may be related to different experimental methods.…”

MTHFR polymorphisms in childhood acute lymphoblastic leukemia: influence on methotrexate therapy

“…From them, only 5 found significant associations with toxicity, but with contradictory results: 2 studies related the T variant allele to a decrease in toxicity risk,24,25 whereas the other 3 associated it to increased risk (Table 1). 26–28…”

“…Mucositis was analyzed in 5 studies, and only Ramírez-Pacheco et al24 concluded that CC genotype was associated with a higher risk of developing mucositis in a cohort of 109 children with ALL. The rest of the 4 studies found no association, in line with our meta-analysis results in which 8 out of 10 studies were not significant.…”

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

“…Polymorphism in genes, coding for these transporters, have been studied for associations with an altered clearance and sensitivity of MTX (e.g. ABCB1 and ABCC4 genes), but results have been inconsistent ( Ramírez-Pacheco et al., 2016 ; Hegyi et al., 2017 ). Genetic polymorphism in the ABC-transporter genes are believed to result in failure of the excretory system, prolonged MTX exposure and have been associated with higher incidence of myelosuppression during MTX treatment ( Mlakar et al., 2016 ).…”

“…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.…”