药物基因组学应用于急性白血病:确定临床相关的遗传变异
Flávia Melo Cunha de Pinho Pessoa1, Isabelle Magalhães Farias1, Beatriz Maria Dias Nogueira1
1Clinical Genetics Laboratory, Department of Medicine, Drug Research and Development Center (NPDM), Federal University of Ceará, Fortaleza 60430-275, CE, Brazil.
Biomedicines
|November 27, 2025
概括
药物基因组变异在急性白血病 (AML和ALL) 中显著影响化疗的有效性和毒性. 识别ABCB1,TPMT和NUDT15等关键遗传标记可以个性化治疗并减少不良事件,从而改善患者的治疗结果.
科学领域:
- 血液学 血液学 血液学
- 药物基因组学 药物基因组学
- 在瘤学瘤学.
背景情况:
- 急性白血病 (AML和ALL) 需要密集化疗,但药物毒性限制了治疗的成功.
- 通过分析遗传变异,药物基因组学提供了一种优化化疗效和最小化毒性的策略.
- 单核酸变体 (SNVs) 可以影响白血病患者的药物代谢,反应和不良事件.
研究的目的:
- 鉴定和分析临床相关的基因变异影响化学疗法反应和毒性在急性髓性白血病 (AML) 和急性淋巴细胞白血病 (ALL).
- 评估白血病患者队伍中特定变异的频率和临床意义,包括ABCB1,TPMT和NUDT15中的变异.
主要方法:
- 利用ClinPGx/PharmGKB数据库对策划,临床注释的遗传变异进行了研究.
- 分析了AML和ALL的变体数据,根据类型 (同义词,非同义词,内在) 和临床意义分类它们.
- 专注于与药物代谢,疗效和毒性相关的变异,包括ABCB1,TPMT,NUDT15,ABCC1,SLC28A3和RARG中的变异.
主要成果:
- 策划了AML的24个变体和ALL的57个变体,在ALL中更频繁的非同义变体和AML的同义变体.
- 在12.5%的AML和10.5%的ALL病例中确定了ABCB1的临床显著变异,这表明在化疗耐药性中发挥了作用.
- 在TPMT,NUDT15,ABCC1,SLC28A3和RARG的相关变体,具有严重的不良事件,如骨髓毒性,粘膜炎,心脏毒性和肝毒性.
结论:
- 遗传变异在调节化疗反应和急性白血病中毒性的过程中起着至关重要的作用.
- ABCB1变种可以作为耐药性标记物,而建议在治疗前对TPMT和NUDT15进行基因定型,以防止严重的毒性.
- 巩固药物遗传学数据和前性验证对于将精准医学纳入常规急性白血病管理至关重要.
相关概念视频
02:50Combination Therapies and Personalized Medicine
5.9K
Combining two or more treatment methods increases the life span of cancer patients while reducing damage to vital organs or tissue from the overuse of a single treatment. Combination therapy also targets different cancer-inducing pathways, thus reducing the chances of developing resistance to treatment.
The combination of the drug acetazolamide and sulforaphane is a good example of combination therapy to treat cancer. The cells in the interior of a large tumor often die due to the hypoxic and...
The combination of the drug acetazolamide and sulforaphane is a good example of combination therapy to treat cancer. The cells in the interior of a large tumor often die due to the hypoxic and...
5.9K
01:11Genome-wide Association Studies-GWAS
15.2K
Genome-wide association studies or GWAS are used to identify whether common SNPs are associated with certain diseases. Suppose specific SNPs are more frequently observed in individuals with a particular disease than those without the disease. In that case, those SNPs are said to be associated with the disease. Chi-square analysis is performed to check the probability of the allele likely to be associated with the disease.
GWAS does not require the identification of the target gene involved in...
GWAS does not require the identification of the target gene involved in...
15.2K