药物遗传学能否影响阿糖胞苷和蒽环类药物对成人急性髓性白血病患者的治疗效果?塞尔维亚的经验。

IF 2 4区 医学 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY Journal of Medical Biochemistry Pub Date : 2024-06-15 DOI:10.5937/jomb0-47459
Zlatko Pravdić, Nada Suvajdžić-Vuković, Marijana Virijević, Mirjana Mitrović, Nikola Pantić, Nikica Sabljić, Đorđe Pavlović, Irena Marjanović, Zoran Bukumirić, Ana Vidović, Ljubomir Jaković, Sonja Pavlović, Vladimir Gašić
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引用次数: 0

摘要

背景:以阿糖胞苷-蒽环类为基础的诱导化疗仍是新诊断急性髓性白血病(AML)患者缓解诱导治疗的标准疗法。急性髓性白血病患者的治疗反应存在明显差异。这一事实的部分原因可能是患者与阿糖胞苷和蒽环类药物代谢途径有关的基因变异。本研究旨在评估药物基因 SLC29A1、DCK、ABCB1、GSTM1 和 GSTT1 的变异以及实验室和 AML 相关参数对成年 AML 患者临床结果的影响:研究共纳入了 100 名急性髓细胞性白血病患者。通过PCR、片段分析和直接测序等方法检测药物基因变异SLC29A1 rs9394992、DCK rs12648166、ABCB1 rs2032582以及GSTM1和GSTT1基因缺失。采用了描述性和分析性统计方法。采用 Kaplan-Meier 法和 Log-Rank 检验法进行生存率分析:这是首次在塞尔维亚人群中开展成人急性髓细胞白血病药物遗传学研究。SLC29A1、DCK、ABCB1和GSTT1以及GSTM1基因中的变异,无论是单独还是组合出现,都不会影响我们队列中急性髓细胞性白血病患者的临床预后。完全缓解被认为是临床结果的独立预后指标:结论:药物遗传学必须考虑特定人群的基因组特征。由于欧洲人群中有关急性髓细胞性白血病药物遗传学的数据有限,我们的研究结果为这一领域的知识做出了贡献,并有力地表明必须采用高通量方法来寻找欧洲人群中急性髓细胞性白血病的特定药物遗传学标志物。
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Can pharmacogenetics impact the therapeutic effect of cytarabine and anthracyclines in adult acute myeloid leukaemia patients?: A Serbian experience.

Background: Cytarabine-anthracycline-based induction chemotherapy remains the standard of care for remission induction among patients with newly diagnosed acute myeloid leukaemia (AML). There are remarkable differences in therapy response among AML patients. This fact could be partly explained by the patients' genetic variability related to the metabolic paths of cytarabine and anthracyclines. This study aims to evaluate the effect of variants in pharmacogenes SLC29A1, DCK, ABCB1, GSTM1, and GSTT1, as well as laboratory and AML-related parameters on clinical outcomes in adult AML patients.

Methods: A total of 100 AML patients were included in the study. Pharmacogenetic variants SLC29A1 rs9394992, DCK rs12648166, ABCB1 rs2032582, and GSTM1 and GSTT1 gene deletions were detected by methodology based on PCR, fragment analysis and direct sequencing. The methods of descriptive and analytic statistics were used. Survival analysis was done using the Kaplan-Meier method using the Log-Rank test.

Results: This is the first study of adult AML pharmacogenetics in the Serbian population. Clinical outcomes in our cohort of AML patients were not impacted by analysed variants in SLC29A1, DCK, ABCB1 and GSTT1, and GSTM1 genes, independently or in combinations. Achievement of complete remission was identified as an independent prognostic indicator of clinical outcome.

Conclusions: The population-specific genomic profile has to be considered in pharmacogenetics. Since the data on AML pharmacogenetics in European populations is limited, our results contribute to knowledge in this field and strongly indicate that a high-throughput approach must be applied to find particular pharmacogenetic markers of AML in the European population.

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来源期刊
Journal of Medical Biochemistry
Journal of Medical Biochemistry BIOCHEMISTRY & MOLECULAR BIOLOGY-
CiteScore
3.00
自引率
12.00%
发文量
60
审稿时长
>12 weeks
期刊介绍: The JOURNAL OF MEDICAL BIOCHEMISTRY (J MED BIOCHEM) is the official journal of the Society of Medical Biochemists of Serbia with international peer-review. Papers are independently reviewed by at least two reviewers selected by the Editors as Blind Peer Reviews. The Journal of Medical Biochemistry is published quarterly. The Journal publishes original scientific and specialized articles on all aspects of clinical and medical biochemistry, molecular medicine, clinical hematology and coagulation, clinical immunology and autoimmunity, clinical microbiology, virology, clinical genomics and molecular biology, genetic epidemiology, drug measurement, evaluation of diagnostic markers, new reagents and laboratory equipment, reference materials and methods, reference values, laboratory organization, automation, quality control, clinical metrology, all related scientific disciplines where chemistry, biochemistry, molecular biology and immunochemistry deal with the study of normal and pathologic processes in human beings.
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