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[急性白血病治疗期间发生感染并发症儿童免疫反应基因的等位基因变体]

[Allelic variants of immune response genes in children with infectious complications during the treatment of acute leukemia].

作者信息

Avdonina M A, Abramov I S, Ammour Y I, Nasedkina T V

机构信息

Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, 119991 Russia.

Rogachev Federal Research Center of Pediatric Hematology, Oncology and Immunology, Moscow, 119117 Russia.

出版信息

Mol Biol (Mosk). 2017 Mar-Apr;51(2):301-307. doi: 10.7868/S0026898417020045.

Abstract

Infectious complications that arise during the treatment of children with acute leukemia with chemotherapeutic agents at high doses represent a serious problem in oncohematology. To find genetic conditions that may lead to the development of postchemotherapy infections, the genomes of 12 children with acute leukemia who had severe infectious complications during therapy were examined. At the same time, the coding regions of 17 genes involved in the regulation of the immune response were determined by massive parallel sequencing. The analysis revealed 39 nonsynonymous SNPs that lead to amino acid substitutions, including the following informative genetic markers: PTPN22 c.1858C>T (rs2476601), TLR4 c.896A>G (rs4986790) and TLR4 c.1196C>T (rs4986791), IL7R c.197T>C (rs1494555) and IL7R c.412G>A (rs1494558). The results of massive parallel sequencing were validated by Sanger sequencing. The identification of genetic markers associated with the predisposition to infectious complications may allow one to assess the individual risk of the severe infection development in children with acute leukemia during the treatment with chemotherapeutic agents and to begin the development of personalized approaches to anticancer therapy.

摘要

在使用高剂量化疗药物治疗儿童急性白血病期间出现的感染性并发症是肿瘤血液学中的一个严重问题。为了找出可能导致化疗后感染发生的遗传条件,对12名在治疗期间出现严重感染性并发症的急性白血病儿童的基因组进行了检测。同时,通过大规模平行测序确定了17个参与免疫反应调节的基因的编码区。分析发现了39个导致氨基酸替换的非同义单核苷酸多态性(SNP),包括以下信息丰富的遗传标记:蛋白酪氨酸磷酸酶非受体型22(PTPN22)基因c.1858C>T(rs2476601)、Toll样受体4(TLR4)基因c.896A>G(rs4986790)和TLR4基因c.1196C>T(rs4986791)、白细胞介素7受体(IL7R)基因c.197T>C(rs1494555)和IL7R基因c.412G>A(rs1494558)。大规模平行测序的结果通过桑格测序进行了验证。识别与感染性并发症易感性相关的遗传标记可能有助于评估急性白血病儿童在接受化疗药物治疗期间发生严重感染的个体风险,并开始开发个性化的抗癌治疗方法。

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