IF 4.5 2区 医学 Q1 ONCOLOGY Translational Oncology Pub Date : 2024-12-16 DOI:10.1016/j.tranon.2024.102194
Jinxia Cao, Bin Hu, Tianqi Li, Dan Fang, Ling Jiang, Jun Wang
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引用次数: 0

摘要

急性髓性白血病(AML)是一种复杂的血液恶性肿瘤,在遗传畸变、细胞组成和临床结果方面具有异质性。这种多样性使开发有效、普遍适用的治疗策略变得更加复杂,并凸显了个性化治疗方法的必要性。在我们的研究中,我们利用公开数据集中的高分辨率单细胞RNA测序技术来剖析急性髓细胞性白血病复杂的细胞结构。这种方法发现了急性髓细胞性白血病患者骨髓样本中多种多样的细胞亚群。通过细致的分析,我们确定了 156 个细胞因子相关的差异表达基因,这些基因强调了急性髓细胞性白血病细胞与其微环境之间微妙的相互作用。利用这个全面的数据集,我们构建了一个基于七个关键细胞因子相关基因的预后风险评分模型:CCL23、IL2RA、IL3RA、IL6R、INHBA、TNFSF15 和 TNFSF18。风险评分模型中 7 个基因的 mRNA 水平有显著差异。该模型在几个独立的急性髓细胞性白血病患者队列中得到了严格验证,展示了其将患者分为不同风险类别的强大预后能力。与低风险患者相比,被归入高风险类别的患者的生存率明显较低,这凸显了该模型的临床意义。此外,我们对免疫环境的深入研究还发现,已确定的风险组之间在免疫细胞浸润和细胞因子信号转导方面存在明显差异,从而揭示了驱动疾病进展和治疗耐药性的潜在免疫介导机制。这项综合分析不仅加深了我们对急性髓细胞性白血病的细胞和分子基础的理解,还引入了一种新型的、临床适用的风险评分模型。这一工具有望提高急性髓细胞性白血病预后评估的精确度,从而为更有针对性、更有效的治疗干预铺平道路。我们的研究结果代表了在急性髓细胞白血病治疗中实现个性化医疗的关键一步,为这一具有挑战性的疾病的研究和治疗优化提供了新的途径。
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Cellular heterogeneity and cytokine signatures in acute myeloid leukemia: A novel prognostic model.

Acute Myeloid Leukemia (AML) is a complex hematological malignancy distinguished by its heterogeneity in genetic aberrations, cellular composition, and clinical outcomes. This diversity complicates the development of effective, universally applicable therapeutic strategies and highlights the necessity for personalized approaches to treatment. In our study, we utilized high-resolution single-cell RNA sequencing from publicly available datasets to dissect the complex cellular landscape of AML. This approach uncovered a diverse array of cellular subpopulations within the bone marrow samples of AML patients. Through meticulous analysis, we identified 156 differentially expressed cytokine-related genes that underscore the nuanced interplay between AML cells and their microenvironment. Leveraging this comprehensive dataset, we constructed a prognostic risk score model based on seven pivotal cytokine-related genes: CCL23, IL2RA, IL3RA, IL6R, INHBA, TNFSF15, and TNFSF18. The mRNA levels of 7 genes in the risk score model have significant different. This model was rigorously validated across several independent AML patient cohorts, showcasing its robust prognostic capability to stratify patients into distinct risk categories. Patients classified under the high-risk category exhibited significantly poorer survival outcomes compared to their low-risk counterparts, underscoring the model's clinical relevance. Additionally, our in-depth investigation into the immune landscape revealed marked differences in immune cell infiltration and cytokine signaling between the identified risk groups, shedding light on potential immune-mediated mechanisms driving disease progression and treatment resistance. This comprehensive analysis not only advances our understanding of the cellular and molecular underpinnings of AML but also introduces a novel, clinically applicable risk score model. This tool holds significant promise for enhancing the precision of prognostic assessments in AML, thereby paving the way for more tailored and effective therapeutic interventions. Our findings represent a pivotal step toward the realization of personalized medicine in the management of AML, offering new avenues for research and treatment optimization in this challenging disease landscape.

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来源期刊
Translational Oncology
Translational Oncology Biochemistry, Genetics and Molecular Biology-Cancer Research
CiteScore
7.20
自引率
2.00%
发文量
314
审稿时长
6-12 weeks
期刊介绍: Translational Oncology publishes the results of novel research investigations which bridge the laboratory and clinical settings including risk assessment, cellular and molecular characterization, prevention, detection, diagnosis and treatment of human cancers with the overall goal of improving the clinical care of oncology patients. Translational Oncology will publish laboratory studies of novel therapeutic interventions as well as clinical trials which evaluate new treatment paradigms for cancer. Peer reviewed manuscript types include Original Reports, Reviews and Editorials.
期刊最新文献
m6A methyltransferase METTL3 promotes non-small-cell lung carcinoma progression by inhibiting the RIG-I-MAVS innate immune pathway. 4'-Demethylpodophyllotoxin functions as a mechanism-driven therapy by targeting the PI3K-AKT pathway in Colorectal cancer. Indirect targeting of MYC and direct targeting in combination with chemotherapies are more effective than direct mono-targeting in triple negative breast cancer. Corrigendum to "ACAT1 suppresses clear cell renal cell carcinoma progression by AMPK mediated fatty acid metabolism" [Transl Oncol 47:102043(Sep 2024) 102043]. Corrigendum to "CDYL loss promotes cervical cancer aggression by increasing PD-L1 expression via the suppression of IRF2BP2 transcription" [Transl Oncol. 2024 Sep;47:102038 /PMID: 38991463].
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