Journal of Leukemia
Open Access

Development of a Novel Acute Myeloid Leukemia Predictive Risk Assessment Using M6a-Related miRNAs

Tatarczuch Maciej^{* *}Correspondence: Tatarczuch Maciej, Department of Medicine, Monash University, Melbourne, Australia, Email:

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Description

The malignant clonal proliferation of immature hematopoietic stem cells in bone marrow and peripheral blood is the source of Acute Myeloid Leukemia (AML), a type of hematological malignancy. AML is one of the top 10 causes of cancer-related deaths due to its high mortality, rapid progression, high heterogenicity, extreme invasiveness, and frequent mutation. For patients with AML, chemotherapy and stem cell transplants continue to be the main therapeutic options. Furthermore, the use of novel kinase inhibitors, monoclonal antibodies, and Chimeric Antigen Receptor (CAR)-T cell therapy, among other novel therapy regimens, has improved the cure rate for Acute Myeloid Leukemia (AML). Still, the overall results fall short of expectations. In order to improve AML patient treatment and prognosis, our study aims to identify prognostic markers and develop a novel risk prediction model. In eukaryotic non-coding RNAs (ncRNAs) and mRNAs, N6-methyladenosine (m6A) modification is the most prevalent post-transcriptional epigenetic modification that can affect RNA stability, translation, splicing, and degradation. Methyltransferases, binding proteins, and demethylases regulate this dynamic, reversible process. Numerous investigations have revealed that m6A modification is essential for the development and spread of tumors, including AML. For instance, research revealed that leukemia cells and Hematopoietic Progenitor Cells (HSPCs) could both have their myeloid differentiation regulated by the m6A methyltransferase METTL3 . IGF2BP2, an m6A reader, stimulated the development of AML and the self-renewal of Leukemia Stem Cells (LSCs), and there was a negative correlation found between high expression of IGF2BP2 and survival. METTL3, an m6A reader, may function as a therapeutic target by inhibiting LSCs and encouraging the growth of HSCs. ALKBH5 demethylase was found to be overexpressed in AML patients and was linked to a dismal prognosis. One type of non-coding RNA called miRNA has the ability to control gene expression by preventing translation from starting and causing mRNA to break down. Tumor biological behavior, such as cell differentiation, proliferation, and metastasis, is significantly influenced by miRNA. MiRNAs have been shown in earlier studies to function as therapeutic and prognostic biomarkers in a variety of cancers. In the meantime, miRNAs also frequently have m6A modification. It has been established that miRNAs and m6A modification have an impact on carcinogenesis. Nevertheless, little research has been done on the role of m6A-modified miRNAs in the control of AML. Using the TCGA database as a reference, we identified miRNAs associated with the m6A regulatory genes and their prognostic significance in AML. We examined the association between the tumor immune microenvironment and clinicopathologic features related to m6A-related miRNAs. Additionally, a risk model for predicting Overall Survival (OS) in patients with AML was developed using miRNAs related to m6A. In the end, we created a regulatory network comprising target genes, miRNAs related to m6A, and m6A regulators. Even with significant advancements in treatment, the survival rate for AML patients is still quite low. As a result, more research is concentrating on additional molecular and pathway mechanisms to investigate prognostic and therapeutic biomarkers for patients with AML. According to earlier research, m6A methylation was the most significant RNA modification. It has the ability to control gene expression and the onset and progression of disease. In addition to controlling in mRNAs, m6A modification is frequently enriched in non-coding RNAs like miRNAs. METTL3, through controlling the primiR221/ 222 process, may facilitate the proliferation of cells in bladder cancer. METTL14 had a beneficial effect on hepatocellular carcinoma survival. It inhibited the spread of the tumor by modifying the pri-miR126 process in a way that was dependent on m6A.miRNA-1266, which targets the demethylase enzyme FTO, was found to be weakly expressed in tissues from colorectal cancer and may be able to stop the growth of cancer cells.