Determination of survival associated genetic biomarkers to discover novel therapeutic targets for acute myeloid leukaemia.

IF 1.9 4区医学 Q3 INFECTIOUS DISEASES

Journal of Chemotherapy Pub Date : 2025-07-05 DOI:10.1080/1120009X.2025.2527464

Cansu Ergun, Yağmur Kiraz, Gizem Ayna Duran

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引用次数: 0

Abstract

Acute myeloid leukemia (AML) is a heterogeneous malignancy specified by clonal proliferation of hematopoietic stem cells. This study identifies novel therapeutics for AML by integrating differential gene expression (DEG) and survival analyses. Publicly available GEO microarray datasets were analyzed, including data from 615 AML patients and 22 healthy controls. Multivariate Cox regression identified hazardous genes impacting survival. Protein-protein interaction networks using CytoScape revealed hub genes such as CCT5, ZBTB16, APP, and PTPN6. Functional enrichment revealed key AML-related pathways, such as PI3K/Akt and NF-kappaB signaling. Drug repurposing using the LINCS L1000CDS2 database highlighted potential therapeutics, including 16-Hydroxytriptolide and Tryptosthin AG-1478, with roles in reversing hazardous gene expression patterns. Additional candidates such as Vemurafenib, Parthenolide and Wortmannin, demonstrated promise as targeted agents. These findings underscore the potential of integrating bioinformatics and drug discovery to identify precision medicine in AML. Further studies are warranted to validate these targets and explore their clinical utility.

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确定与生存相关的遗传生物标志物，以发现急性髓性白血病的新治疗靶点。

急性髓系白血病（AML）是一种由造血干细胞克隆性增殖引起的异质性恶性肿瘤。本研究通过整合差异基因表达（DEG）和生存分析来确定AML的新疗法。公开的GEO微阵列数据集被分析，包括来自615名AML患者和22名健康对照者的数据。多变量Cox回归确定了影响生存的危险基因。使用CytoScape的蛋白-蛋白相互作用网络揭示了中心基因，如CCT5、ZBTB16、APP和PTPN6。功能富集揭示了关键的aml相关通路，如PI3K/Akt和NF-kappaB信号通路。使用LINCS L1000CDS2数据库的药物再利用突出了潜在的治疗药物，包括16-羟基雷公素和色氨酸AG-1478，它们在逆转危险基因表达模式中发挥作用。其他候选药物，如Vemurafenib、Parthenolide和Wortmannin，显示出作为靶向药物的希望。这些发现强调了整合生物信息学和药物发现以确定AML精准药物的潜力。需要进一步的研究来验证这些靶点并探索其临床应用。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Journal of Chemotherapy 医学-药学

CiteScore

3.70

自引率

0.00%

发文量

144

审稿时长

6-12 weeks

期刊介绍： The Journal of Chemotherapy is an international multidisciplinary journal committed to the rapid publication of high quality, peer-reviewed, original research on all aspects of antimicrobial and antitumor chemotherapy. The Journal publishes original experimental and clinical research articles, state-of-the-art reviews, brief communications and letters on all aspects of chemotherapy, providing coverage of the pathogenesis, diagnosis, treatment, and control of infection, as well as the use of anticancer and immunomodulating drugs. Specific areas of focus include, but are not limited to: · Antibacterial, antiviral, antifungal, antiparasitic, and antiprotozoal agents; · Anticancer classical and targeted chemotherapeutic agents, biological agents, hormonal drugs, immunomodulatory drugs, cell therapy and gene therapy; · Pharmacokinetic and pharmacodynamic properties of antimicrobial and anticancer agents; · The efficacy, safety and toxicology profiles of antimicrobial and anticancer drugs; · Drug interactions in single or combined applications; · Drug resistance to antimicrobial and anticancer drugs; · Research and development of novel antimicrobial and anticancer drugs, including preclinical, translational and clinical research; · Biomarkers of sensitivity and/or resistance for antimicrobial and anticancer drugs; · Pharmacogenetics and pharmacogenomics; · Precision medicine in infectious disease therapy and in cancer therapy; · Pharmacoeconomics of antimicrobial and anticancer therapies and the implications to patients, health services, and the pharmaceutical industry.