Aml-459 genetic landscape in primary acute myeloid leukemia (aml) and relation with wilms tumor 1 (wt-1) gene expression

Abstract

Context Acute myeloid leukemia (AML) involves abnormal differentiation and clonal proliferation of myeloid progenitor cells in the bone marrow. The Wilms tumor 1 (WT-1) gene regulates cell growth, apoptosis, and differentiation, but its biological role in AML is poorly understood. Objectives Evaluation of RNA expression and molecular functions of WT-1 gene in the context of other genetic alterations in AML. Design Prospective clinical research Setting Tertiary cancer care referral center Patients or Other Participants A total of 112 diagnosed cases of AML, having blast percentage of ≥20% blasts in peripheral blood or bone marrow on Day-0 and treated with induction therapy for 28 days were enrolled. Materials and Methods WT-1 gene expression was assessed using RNA extracted from blood/bone marrow samples. The molecular functions of WT-1 were analyzed by performing gene set enrichment analysis (GSEA), and the relationship of WT-1 expression with immune checkpoints was analyzed using the Sangerbox 3.0 database. Kaplan–Meier survival analysis was performed to estimate the prognostic significance of the WT-1 gene in AML. Results Out of 112 patients, 73 were males, and 39 were females. A total of 97 (86.60%) cases showed increased expression of the WT-1 gene at Day-0 as compared to cases in complete remission (P=<0.001). WT-1 expression was inversely correlated with normal hematopoiesis and positively correlated with age, high marrow blast counts, M4 subtype, and inferior outcomes compared to patients with low WT-1 expression levels. In GSEA, the WT-1 gene displayed an important role in misregulating DNA-binding transcription factor activity, RNA and protein binding, as well as negative regulation of cell growth and cell population proliferation. In immune checkpoint analysis, WT-1 gene expression was positively correlated with CD28, CD40, CD44, CD48, CD80, CD70, CD27, CD86. In survival analysis, poorer overall survival was seen in patients having higher WT-1 gene expression. Conclusions Increased expression of the WT-1 gene positively correlates with the leukemic burden in most cases of AML. The gene can be considered a promising molecular marker for early diagnosis, MRD detection, and a target for developing novel therapeutic approaches against AML.