Cancers · 2025
RNA Sequencing Identifies WT1 Overexpression as a Predictor of Poor Outcomes in Acute Myeloid Leukemia.
СтатьяНазвание и аннотация: Перевод пока не подготовлен
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Goel Harsh, Pandey Avanish Kumar, Kumar Rahul, Kumar Rakesh, Ningombam Somorjit Singh, Naz Farhat, Makkar Harshita, Singh Jay, Ali Shadab, Chopra Anita, Ranjan Amar, Gupta Aditya Kumar, Meena Jagdish Prasad, Viswanathan Ganesh Kumar, Bakhshi Sameer, Sahoo Ranjit Kumar, Batra Atul, Rath Goura Kishor, Hussain Showket, Jha Abhimanyu Kumar, Tanwar Pranay
Аннотация
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.
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.