常见宿主基因组变异在儿童急性淋巴细胞白血病中的作用
Theis Mikkelsen1, Marianne Helenius1, Mirella Ampatzidou2
1Department of Childhood and Adolescent Medicine, Rigshospitalet, Copenhagen, Denmark.
Leukemia
|December 9, 2025
概括
生殖系遗传变异影响儿童急性淋巴细胞白血病 (ALL) 风险和治疗反应. 弥合遗传发现和临床实践之间的差距需要解决改善患者护理的关键翻译障碍.
科学领域:
- 遗传学 是一个遗传学.
- 在瘤学瘤学.
- 药物基因组学 药物基因组学
背景情况:
- 儿童急性淋巴细胞白血病 (ALL) 具有遗传多样性,体质变化指导治疗.
- 生殖系变异,特别是常见的变异,越来越多地与ALL敏感性,治疗疗效和毒性有关,但很少在临床上实施.
- TPMT和NUDT15变种是少数在临床实践中广泛使用的变种之一.
研究的目的:
- 审查从发现到儿童期临床应用的生殖系遗传变异的翻译 ALL.
- 确定影响遗传发现临床实施的关键因素.
- 概述克服临床翻译障碍的策略.
主要方法:
- 对与ALL相关的常见生殖系变异研究的综述.
- 对临床转化至关重要的因素的分析:表型严重性/稀有性,临床效用和干预可用性.
- 讨论障碍:效果大小,人群复制和治疗修改策略.
- 探索解决方案:大规模合作,多基因风险评分和机器学习.
主要成果:
- 许多常见的生殖系变异与ALL有关,但很少有临床可行的变异.
- 临床转换取决于变体的影响,临床效用和干预措施的可用性.
- 障碍包括小效果大小,缺乏多样化的人口数据和未定义的治疗策略.
结论:
- 将儿童ALL的生殖系遗传发现转化为临床实践需要克服重大障碍.
- 大规模的国际合作和先进的生物信息学对于产生强有力的证据至关重要.
- 实施遗传洞察力可以增强个性化治疗策略,改善儿科白血病患者的治疗结果.
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