Lauzon-Young Carolyn, Silva Ananilia, Sadikovic Bekim
Verspeeten Clinical Genome Centre, London Health Sciences Centre, London, ON, Canada.
Pathology and Laboratory Medicine, Western University, London, ON, Canada.
Mol Cytogenet. 2025 Apr 12;18(1):9. doi: 10.1186/s13039-025-00712-9.
Hematologic malignancies (HMs) encompass a diverse spectrum of cancers originating from the blood, bone marrow, and lymphatic systems, with myeloid malignancies representing a significant and complex subset. This review provides a focused analysis of their classification, prevalence, and incidence, highlighting the persistent challenges posed by their intricate genetic and epigenetic landscapes in clinical diagnostics and therapeutics. The genetic basis of myeloid malignancies, including chromosomal translocations, somatic mutations, and copy number variations, is examined in detail, alongside epigenetic modifications with a specific emphasis on DNA methylation. We explore the dynamic interplay between genetic and epigenetic factors, demonstrating how these mechanisms collectively shape disease progression, therapeutic resistance, and clinical outcomes. Advances in diagnostic modalities, particularly those integrating epigenomic insights, are revolutionizing the precision diagnosis of HMs. Key approaches such as nano-based contrast agents, optical imaging, flow cytometry, circulating tumor DNA analysis, and somatic mutation testing are discussed, with particular attention to the transformative role of machine learning in epigenetic data analysis. DNA methylation episignatures have emerged as a pivotal tool, enabling the development of highly sensitive and specific diagnostic and prognostic assays that are now being adopted in clinical practice. We also review the impact of computational advancements and data integration in refining diagnostic and therapeutic strategies. By combining genomic and epigenomic profiling techniques, these innovations are accelerating biomarker discovery and clinical translation, with applications in precision oncology becoming increasingly evident. Comprehensive genomic datasets, coupled with artificial intelligence, are driving actionable insights into the biology of myeloid malignancies and facilitating the optimization of patient management strategies. Finally, this review emphasizes the translational potential of these advancements, focusing on their tangible benefits for patient care and outcomes. By synthesizing current knowledge and recent innovations, we underscore the critical role of precision medicine and epigenomic research in transforming the diagnosis and treatment of myeloid malignancies, setting the stage for ongoing advancements and broader clinical implementation.
血液系统恶性肿瘤(HMs)涵盖了源自血液、骨髓和淋巴系统的多种癌症,其中髓系恶性肿瘤是一个重要且复杂的子集。本综述对其分类、患病率和发病率进行了重点分析,强调了其复杂的遗传和表观遗传格局在临床诊断和治疗中带来的持续挑战。详细研究了髓系恶性肿瘤的遗传基础,包括染色体易位、体细胞突变和拷贝数变异,以及表观遗传修饰,特别强调了DNA甲基化。我们探讨了遗传和表观遗传因素之间的动态相互作用,展示了这些机制如何共同塑造疾病进展、治疗耐药性和临床结果。诊断方式的进展,尤其是那些整合了表观基因组学见解的进展,正在彻底改变血液系统恶性肿瘤的精准诊断。讨论了基于纳米的造影剂、光学成像、流式细胞术、循环肿瘤DNA分析和体细胞突变检测等关键方法,特别关注机器学习在表观遗传数据分析中的变革性作用。DNA甲基化表观特征已成为一种关键工具,能够开发出高度敏感和特异的诊断及预后检测方法,目前已在临床实践中得到应用。我们还回顾了计算进展和数据整合对优化诊断和治疗策略的影响。通过结合基因组和表观基因组分析技术,这些创新正在加速生物标志物的发现和临床转化,在精准肿瘤学中的应用越来越明显。全面的基因组数据集与人工智能相结合,正在推动对髓系恶性肿瘤生物学的可操作见解,并促进患者管理策略的优化。最后,本综述强调了这些进展的转化潜力,重点关注它们对患者护理和结果的实际益处。通过综合当前知识和最新创新,我们强调了精准医学和表观基因组研究在改变髓系恶性肿瘤的诊断和治疗方面的关键作用,为持续进展和更广泛的临床应用奠定了基础。