Influence of Genetic Variations in miRNA and Genes Encoding Proteins in the miRNA Synthesis Complex on Toxicity of the Treatment of Pediatric B-Cell ALL in the Brazilian Amazon

Acute lymphoblastic leukemia (ALL) is the most common childhood cancer in the world. Single nucleotide variants (SNVs) in miRNA and genes encoding proteins of the miRNA synthesis complex (SC) may affect the processing of drugs used in the treatment of ALL, resulting in treatment-related toxicities (TRTs). We investigated the role of 25 SNVs in microRNA genes and genes encoding proteins of the miRNA SC, in 77 patients treated for ALL-B from the Brazilian Amazon. The 25 SNVs were investigated using the TaqMan(R) OpenArray (TM) Genotyping System. SNVs rs2292832 (MIR149), rs2043556 (MIR605), and rs10505168 (MIR2053) were associated with an increased risk of developing Neurological Toxicity, while rs2505901 (MIR938) was associated with protection from this toxicity. MIR2053 (rs10505168) and MIR323B (rs56103835) were associated with protection from gastrointestinal toxicity, while DROSHA (rs639174) increased the risk of development. The rs2043556 (MIR605) variant was related to protection from infectious toxicity. SNVs rs12904 (MIR200C), rs3746444 (MIR499A), and rs10739971 (MIRLET7A1) were associated with a lower risk for severe hematologic toxicity during ALL treatment. These findings reveal the potential for the use of these genetic variants to understand the development of toxicities related to the treatment of ALL in patients from the Brazilian Amazon region.

Automated summary

This study investigated the role of genetic variations in miRNA genes and genes encoding proteins of the miRNA synthesis complex (SC) in the treatment-related toxicities (TRTs) of acute lymphoblastic leukemia (ALL) patients. The findings revealed several SNVs associated with increased or decreased risk of developing different toxicities, such as neurological toxicity, gastrointestinal toxicity, infectious toxicity, and severe hematologic toxicity. The study suggests the potential use of these genetic variants to understand and predict the development of toxicities in ALL patients from the Brazilian Amazon region.