干扰素信号预测急性髓性白血病化疗耐药。

IF 7.5 2区医学 Q1 MEDICINE, RESEARCH & EXPERIMENTAL

Biomedicine & Pharmacotherapy Pub Date : 2025-10-01 DOI:10.1016/j.biopha.2025.118612

Ela Cerovska , David Kundrat , Zdenek Krejcik , Cyril Salek , Jan Musil , Eliska Cechova , Michaela Dostalova Merkerova , Monika Belickova , Hana Remesova

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引用次数: 0

摘要

背景：尽管治疗发展取得了进展，蒽环类-阿糖胞苷诱导方案仍然是急性髓性白血病（AML）治疗的金标准。然而，评估治疗敏感性、调整治疗强度和指导实验性治疗使用的可靠预测标志物仍然缺乏。本研究旨在建立AML化疗耐药的预测模型。方法：对白血病原细胞进行转录组测序和DNA甲基化分析，以鉴定反应（RES）和非反应（non-RES）患者之间差异表达和甲基化基因。使用获得的数据建立逻辑回归模型来预测完全缓解（CR），并进一步验证。结果：与RES患者相比，非RES患者在诊断时表现出干扰素相关DNA损伤抵抗特征（IRDS）基因的显著过表达。基于三个IRDS基因（IFIT5, IFI44L, IFI44）的表达，我们开发了IRDS评分，该评分具有很高的预测准确性，计算出RES患者的CR概率为0.71，非RES患者的CR概率为0.31。治疗后组蛋白和染色质重塑基因的下调是成功治疗反应的标志。整合分析显示，1108个基因在RES和非RES患者之间的基因表达和DNA甲基化变化一致，包括IRDS基因IFIT5和IFI44L。结论：基于IRDS评分的模型预测AML化疗耐药具有较高的准确性和可行性。这种方法快速、成本有效，而且需要现成的生物材料。该工具有望指导治疗决策，并确定强化或实验性治疗的候选者。

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Interferon signature predicts chemotherapy resistance in acute myeloid leukaemia

Background

Despite advances in therapeutic development, an anthracycline-cytarabine induction regimen remains the gold standard for acute myeloid leukaemia (AML) treatment. However, reliable predictive markers for assessing treatment sensitivity, adjusting therapy intensity, and guiding the use of experimental therapies are still lacking. This study aimed to develop a predictive model of AML chemoresistance.

Methods

Transcriptome sequencing and DNA methylation analysis of leukaemic blasts were performed to identify differentially expressed and methylated genes between responding (RES) and non-responding (non-RES) patients. A logistic regression nomogram model was developed using obtained data to predict complete remission (CR) and was further validated.

Results

Compared to RES patients, non-RES patients exhibited a significant overexpression of interferon-related DNA damage resistance signature (IRDS) genes at diagnosis. Based on the expression of three IRDS genes (IFIT5, IFI44L, IFI44), we developed the IRDS score, which demonstrated high predictive accuracy, with calculated probabilities of CR of 0.71 for RES patients and 0.31 for non-RES patients. Downregulation of histone and chromatin remodelling genes following therapy administration was a hallmark of a successful treatment response. Integrative analysis revealed 1108 genes with concordant changes in both gene expression and DNA methylation between RES and non-RES patients, including IRDS genes IFIT5 and IFI44L.

Conclusions

The IRDS score-based model predicts AML chemoresistance with high accuracy and feasibility. It is quick, cost effective, and requires readily available biological material. This tool shows promise for guiding treatment decisions and identifying candidates for intensified or experimental therapies.

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来源期刊

Biomedicine & Pharmacotherapy 医学-药学

CiteScore

11.90

自引率

2.70%

发文量

1621

审稿时长

48 days

期刊介绍： Biomedicine & Pharmacotherapy stands as a multidisciplinary journal, presenting a spectrum of original research reports, reviews, and communications in the realms of clinical and basic medicine, as well as pharmacology. The journal spans various fields, including Cancer, Nutriceutics, Neurodegenerative, Cardiac, and Infectious Diseases.