Background/Objectives:Gene rearrangements involving oncogenes are major drivers in acute leukemia, influencing disease classification, prognosis, and therapeutic decision-making. Targeted RNA sequencing (RNA-Seq) panels capable of detecting intergenic and intragenic fusions across multiple genes are increasingly used in diagnostic settings. However, comparative evaluation with orthogonal technologies remains limited.Material and Methods: We compared the performance of a 108-gene anchored multiplex PCR (AMP)-based RNA-Seq panel with that of Optical Genome Mapping (OGM) in 467 acute leukemia cases. The cohort included 360 cases of acute myeloid leukemia (AML), 89 B-lymphoblastic leukemia (B-ALL), 12 T-lymphoblastic leukemia (T-ALL), and 6 cases of mixed phenotype acute leukemia (MPAL).Results:Results of both methods were concordant in 175 (74.7%) of 234 detected gene/rearrangement fusions. The concordance rate varied significantly across different leukemia types, ranging from 80.2% in B-ALL to 41.7% in T-ALL (p< 0.001) OGM uniquely detected 37 of 234 (15.8%) clinically relevant rearrangements, whereas RNA-Seq exclusively identified 22 of 234 (9.4%). Enhancer-hijacking lesions, includingMECOMandBCL11Brearrangements,CDK6::MNX1, andIGHrearrangements, had a markedly lower concordance (20.6%) compared with all other aberrations (93.1%) (p< 0.001). Conversely, some gene fusions arising from intrachromosomal deletions were interpreted by OGM as simple deletions rather than rearrangements or fusions.Conclusions:Targeted RNA-Seq was effective for detecting chimeric fusion transcripts and showed slightly better performance in identifying fusions resulting from deletions. However, OGM was effective for detecting enhancer-hijacking events that do not generate fusion transcripts. Both methods are complementary for the workup of acute leukemia cases.
背景/目的：涉及癌基因的基因重排是急性白血病的主要驱动因素，影响疾病分类、预后和治疗决策。能够检测多基因间和基因内融合的靶向RNA测序（RNA-Seq）检测组合在诊断环境中应用日益广泛，但其与正交技术的比较评估仍有限。 材料与方法：我们在467例急性白血病病例中，比较了基于108基因锚定多重PCR（AMP）的RNA-Seq检测组合与光学基因组图谱（OGM）技术的检测性能。该队列包括360例急性髓系白血病（AML）、89例B淋巴细胞白血病（B-ALL）、12例T淋巴细胞白血病（T-ALL）和6例混合表型急性白血病（MPAL）。 结果：在检测到的234个基因/重排融合中，两种方法的结果在175例（74.7%）中一致。不同白血病类型间的一致性率差异显著，从B-ALL的80.2%到T-ALL的41.7%（p < 0.001）。OGM独特检测到234例中37例（15.8%）具有临床相关性的重排，而RNA-Seq则独特检测到22例（9.4%）。与所有其他异常（93.1%）相比，包括MECOM和BCL11B重排、CDK6::MNX1以及IGH重排在内的增强子劫持病变的一致性率显著较低（20.6%）（p < 0.001）。相反，一些由染色体内缺失引起的基因融合被OGM解读为简单缺失而非重排或融合。 结论：靶向RNA-Seq在检测嵌合融合转录本方面有效，且在识别由缺失引起的融合方面表现略优。然而，OGM在检测不产生融合转录本的增强子劫持事件方面有效。两种方法在急性白血病病例的检查中具有互补性。
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