AML-016 Genetic, Epigenetic, and Clinical Significance of Wilms’ Tumor 1 (WT-1) Gene in Acute Myeloid Leukemia

• Published in: Clinical lymphoma, myeloma and leukemia Vol. 24; pp. S287 - S288
• Main Authors: Goel, Harsh, Chopra, Anita, Ranjan, Amar, Gupta, Aditya Kumar, Meena, Jagdish Prasad, Viswanathan, Ganesh Kumar, Bakhshi, Sameer, Khan, Maroof Ahmad, Tanwar, Pranay
• Format: Journal Article
• Language: English
• Published: Elsevier Inc 01.09.2024
• Subjects: AML; gene expression; methylation; WT-1; AML; WT-1; methylation; gene expression
• ISSN: 2152-2650
• DOI: 10.1016/S2152-2650(24)01146-7

Acute myeloid leukemia (AML) is a genetically intricate hematologic malignancy characterized by aberrant differentiation and proliferation of myeloid progenitor cells in the bone marrow. The Wilms’ tumor 1 (WT-1) gene serves as a crucial regulator of malignant hematopoiesis, modulating cell growth, apoptosis, and differentiation through its zinc-finger transcription factor activity. Despite its importance, the epigenetic and clinical significance of WT-1 in AML remains elusive. This study aims to investigate the RNA expression, methylation levels, and molecular functions of the WT-1 gene in AML. This prospective clinical research was performed in our institution from 2020-2024. Bone marrow (BM) and peripheral blood (PB) samples were collected from 174 AML cases at diagnosis, 143 post-induction chemotherapy, and 20 nonmalignant controls. WT-1 gene expression and promoter methylation status were evaluated using reverse transcriptionpolymerase chain reaction (RT-PCR) and methylation-specific PCR (MS-PCR). Additionally, molecular and biological functions of WT-1 were explored through Gene Set Enrichment Analysis (GSEA), and its relationship with immune checkpoint analysis was assessed using the Sangerbox database. A flow cytometric immunophenotyping study was also performed using a panel of monoclonal antibodies specific to AML. Among the 174 subjects studied, 82.43% exhibited WT-1 gene overexpression at diagnosis compared to cases in complete remission or controls (P<0.001). Furthermore, robust hypermethylation of the WT-1 promoter was observed in 75.67% of AML cases at diagnosis (P<0.001). WT-1 expression and methylation levels were inversely correlated with normal hematopoiesis and positively associated with age, high marrow blast counts, adverse risk cytogenetics, and inferior outcomes. GSEA revealed WT-1’s involvement in transcription misregulation of cancer and various molecular functions related to cell growth, proliferation, and apoptosis. Additionally, WT-1 expression positively correlated with immune checkpoint markers such as CD28, CD40, and CD86. The flow cytometric immunophenotyping study demonstrated that CD34, CD45, CD117, CD38, and CD56 were expressed as positive in most cases, while cCD79a, CD19, CD7, cCD3, CD123, CD11b were negatively observed. Overexpression and hypermethylation of WT-1 are associated with increased leukemic burden in AML, suggesting its potential as a molecular marker for early diagnosis, minimal residual disease detection, and a therapeutic target against AML.