Background/Objectives: AML is a heterogeneous hematological malignancy distinguished by the clonal expansion of immature myeloid progenitor cells. Despite advances in therapy, relapse rates remain high, and outcomes are poor. The WT1 gene has emerged as a potential contributor to leukemogenesis, but its clinical relevance at the transcriptional level is not fully understood. This study employed RNA sequencing as a discovery tool to identify WT1 gene expression in AML and further investigated its role in diagnosis, prognosis, and treatment response. Methods: Between 2020 and 2024, 345 diagnostic, 259 post-induction, and 70 relapse-stage BM or PB samples were prospectively collected from de novo AML patients at AIIMS, New Delhi. RNA sequencing was initially performed on five paired diagnosis-relapse samples to profile transcriptomic changes and assess WT1 expression dynamics. WT1 expression was further validated by qPCR. The relationship between WT1 expression and various clinical parameters was evaluated using Cox regression analysis to determine its impact on prognosis. Results: RNA sequencing and qPCR confirmed WT1 overexpression at diagnosis, which significantly declined following induction therapy. High WT1 expression at diagnosis was linked with adverse clinical characteristics, including elevated WBC counts and higher blast percentages and predicted poor survival outcomes. WT1 expression was identified as a significant prognostic marker, correlating with OS and EFS. Conclusions: By integrating RNA sequencing with targeted validation, this study highlights WT1 expression as a critical biomarker for AML diagnosis, prognosis, and treatment response. The findings suggest that WT1 expression may serve as a valuable tool for monitoring disease status, risk stratification, and guiding treatment decisions in AML, with potential applications for WT1-targeted precision therapies.
背景/目的：急性髓系白血病（AML）是一种异质性血液系统恶性肿瘤，其特征为未成熟髓系祖细胞的克隆性扩增。尽管治疗方法有所进展，但复发率仍然较高，预后较差。WT1基因已被证实是白血病发生过程中的潜在驱动因素，但其在转录水平的临床意义尚未完全阐明。本研究采用RNA测序作为探索工具，检测AML中WT1基因的表达情况，并进一步探讨其在诊断、预后及治疗反应评估中的作用。方法：2020年至2024年间，前瞻性收集了来自新德里全印医学科学研究所的345例初诊、259例诱导治疗后及70例复发期AML患者的骨髓或外周血样本。首先对5对初诊-复发配对样本进行RNA测序，以描绘转录组变化并评估WT1表达动态。通过qPCR进一步验证WT1表达水平。采用Cox回归分析评估WT1表达与各项临床参数的关系，以确定其对预后的影响。结果：RNA测序与qPCR结果均证实WT1在初诊时呈过表达状态，且在诱导治疗后显著下降。初诊时的高WT1表达与不良临床特征相关，包括白细胞计数升高、原始细胞比例增高，并预示较差的生存结局。WT1表达被确定为重要的预后标志物，与总生存期和无事件生存期显著相关。结论：通过整合RNA测序与靶向验证，本研究揭示WT1表达可作为AML诊断、预后评估及治疗反应监测的关键生物标志物。研究结果表明，WT1表达水平可作为监测疾病状态、风险分层及指导AML治疗决策的重要工具，并为WT1靶向精准治疗提供了潜在应用方向。
肿瘤(癌症)患者之家