Background:Acute lymphoblastic leukemia (ALL) is a genetically heterogeneous malignancy driven by structural variants (SVs) that impact diagnosis, prognosis, and treatment. Traditional methods such as karyotyping, FISH, and PCR often fail to detect cryptic or complex rearrangements, which are critical for accurate risk stratification.Methods:Optical Genome Mapping (OGM) is a technology that directly analyzes ultra-high-molecular-weight DNA, enabling the identification of balanced and unbalanced SVs, copy number variations (CNVs), and gene fusions with high resolution. This review compares the advantages and limitations of OGM versus standard techniques in ALL.Results:OGM improves ALL diagnosis by detecting clinically relevant alterations such asIKZF1deletions, crypticKMT2Arearrangements, and kinase fusions, especially in cases with normal or uninformative karyotypes. It reduces artifacts by eliminating cell culture and shortens reporting times. OGM resolves complex events like intrachromosomal amplifications and chromothripsis, enhancing classification and therapy decisions. Limitations include reduced sensitivity in repetitive regions, challenges in detecting Robertsonian translocations, difficulties with complex ploidies, and lower sensitivity for low-frequency subclones.Conclusions:Integrating OGM with next-generation sequencing (NGS) allows comprehensive genomic profiling, improving diagnosis, prognosis, and personalized treatment in ALL. Future advancements promise to further enhance the clinical utility of OGM.
背景：急性淋巴细胞白血病（ALL）是一种由结构变异（SVs）驱动的遗传异质性恶性肿瘤，这些变异影响诊断、预后和治疗。传统的核型分析、荧光原位杂交（FISH）和聚合酶链式反应（PCR）等方法常无法检测到隐匿性或复杂的重排，而这些重排对于准确的风险分层至关重要。 方法：光学基因组图谱（OGM）是一种直接分析超高分子量DNA的技术，能够以高分辨率识别平衡与非平衡结构变异、拷贝数变异（CNVs）及基因融合。本综述比较了OGM与标准技术在ALL应用中的优势与局限性。 结果：OGM通过检测临床相关改变（如IKZF1缺失、隐匿性KMT2A重排及激酶融合等）改善了ALL的诊断，尤其适用于核型正常或信息不足的病例。该技术通过避免细胞培养减少了人为假象，并缩短了报告时间。OGM能够解析复杂事件，如染色体内扩增和染色体碎裂，从而优化疾病分类与治疗决策。其局限性包括在重复区域的灵敏度降低、罗伯逊易位检测困难、复杂倍体分析存在挑战以及对低频亚克隆的敏感性较低。 结论：将OGM与下一代测序（NGS）技术结合，可实现全面的基因组分析，从而改善ALL的诊断、预后判断及个体化治疗。未来的技术进步有望进一步提升OGM的临床应用价值。
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