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miRNA 及其编码蛋白在 miRNA 合成复合物中的基因遗传变异对巴西亚马逊地区儿科 B 细胞急性淋巴细胞白血病治疗毒性的影响。

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.

机构信息

Oncology Research Center, Federal University of Pará, Belém 66073-005, PA, Brazil.

Otávio Lobo Children's Cancer Hospital, Belém 66063-005, PA, Brazil.

出版信息

Int J Mol Sci. 2023 Feb 23;24(5):4431. doi: 10.3390/ijms24054431.

Abstract

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 OpenArray™ Genotyping System. SNVs rs2292832 (), rs2043556 (), and rs10505168 () were associated with an increased risk of developing Neurological Toxicity, while rs2505901 () was associated with protection from this toxicity. (rs10505168) and (rs56103835) were associated with protection from gastrointestinal toxicity, while (rs639174) increased the risk of development. The rs2043556 () variant was related to protection from infectious toxicity. SNVs rs12904 (), rs3746444 (), and rs10739971 () 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.

摘要

急性淋巴细胞白血病 (ALL) 是世界上最常见的儿童癌症。miRNA 及其编码 miRNA 合成复合物 (SC) 蛋白的基因中的单核苷酸变异 (SNV) 可能会影响 ALL 治疗中使用的药物的处理,从而导致治疗相关毒性 (TRTs)。我们调查了 25 个 miRNA 基因和 miRNA SC 蛋白编码基因中的 SNV 在 77 名来自巴西亚马逊地区 ALL-B 治疗患者中的作用。使用 TaqMan OpenArray™ 基因分型系统研究了 25 个 SNV。SNV rs2292832 ()、rs2043556 () 和 rs10505168 () 与发生神经毒性的风险增加相关,而 rs2505901 () 与保护免受这种毒性相关。rs10505168 () 和 rs56103835 () 与保护免受胃肠道毒性相关,而 rs639174 () 增加了发生的风险。rs2043556 () 变异与保护免受感染毒性相关。SNV rs12904 ()、rs3746444 () 和 rs10739971 () 与 ALL 治疗期间严重血液毒性的风险降低相关。这些发现揭示了这些遗传变异在理解巴西亚马逊地区患者 ALL 治疗相关毒性发展中的潜在用途。

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Mol Biol Rep. 2021 Jan;48(1):817-822. doi: 10.1007/s11033-020-06073-3. Epub 2021 Jan 13.

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