Perspective - (2025)Volume 7, Issue 1
Epigenetic biomarkers are transforming Acute Myeloid Leukemia (AML) diagnosis, prognosis, and treatment selection, enabling personalized therapeutic approaches that improve patient outcomes. Acute Myeloid Leukemia (AML) is a heterogeneous hematologic malignancy characterized by the accumulation of immature myeloid cells in the bone marrow. Despite advances in treatment, the five-year survival rate remains approximately 25%, highlighting the need for improved therapeutic strategies. Epigenetic alterations play fundamental roles in AML pathogenesis and represent promising targets for precision medicine approaches.
DNA methylation patterns serve as powerful biomarkers for AML classification and prognosis. The CpG Island Methylator Phenotype (CIMP) has been identified in approximately 20% of AML cases and is associated with distinct clinical characteristics and treatment responses. CIMP-positive AML patients show extensive hypermethylation of tumor suppressor genes and respond favorably to DNA methyltransferase inhibitors such as azacitidine and decitabine.
The methylation status of specific genes provides prognostic information in AML. Hypermethylation of the CDKN2B promoter is associated with poor prognosis and resistance to conventional chemotherapy. Conversely, methylation of the CEBPA promoter, while reducing gene expression, paradoxically correlates with better outcomes in certain AML subtypes. These methylation biomarkers can guide treatment selection and risk stratification.
Mutations in epigenetic regulators are common in AML and serve as important biomarkers. TET2 mutations occur in approximately 20% of AML cases and are associated with hypermethylation and poor prognosis. However, TET2-mutated AML patients show enhanced sensitivity to hypomethylating agents, providing a clear therapeutic target. Similarly, mutations in DNMT3A, occurring in 25% of AML cases, confer adverse prognosis but may predict response to specific epigenetic therapies.
The Isocitrate Dehydrogenase (IDH) mutations, present in approximately 20% of AML cases, create unique epigenetic landscapes through the production of the oncometabolite 2-Hydroxyglutarate (2-HG). 2-HG inhibits TET enzymes and α-ketoglutarate-dependent dioxygenases, leading to hypermethylation and differentiation block. IDH-mutated AML patients show excellent responses to IDH inhibitors such as ivosidenib and enasidenib, making IDH mutation status a critical biomarker for treatment selection.
Histone modifications serve as additional biomarkers in AML. The Lysine-Specific Demethylase 1 (LSD1) is overexpressed in approximately 70% of AML cases and correlates with poor prognosis. LSD1 maintains the stem cell characteristics of leukemic cells by regulating the expression of differentiation-related genes. LSD1 inhibitors have shown promise in clinical trials, particularly in combination with standard chemotherapy.
The Mixed Lineage Leukemia (MLL) gene is involved in chromosomal translocations in approximately 10% of AML cases, creating fusion proteins that recruit histone methyltransferases and cause aberrant gene expression. MLL-rearranged AML has distinct clinical characteristics and poor prognosis with conventional therapy. However, these patients show enhanced sensitivity to DOT1L inhibitors, which target the histone methyltransferase recruited by MLL fusion proteins.
MicroRNA expression profiles provide valuable prognostic information in AML. High expression of miR-3151 is associated with poor prognosis and chemotherapy resistance, while high miR-181a expression correlates with favorable outcomes. The integration of miRNA profiling with other molecular markers improves risk stratification and treatment selection.
Long non-coding RNAs (lncRNAs) are emerging as important biomarkers in AML. The lncRNA HOTAIRM1 is specifically expressed in myeloid cells and is downregulated in AML with NPM1 mutations. HOTAIRM1 expression levels correlate with differentiation status and treatment response, making it a potential biomarker for monitoring therapeutic efficacy.
The clinical implementation of epigenetic biomarkers in AML requires standardized assays and clear treatment guidelines. Several commercial assays are now available for detecting IDH mutations, and methylation profiling is being integrated into clinical practice. The development of rapid, cost-effective assays for epigenetic biomarker detection is essential for widespread adoption.
Combination therapies targeting multiple epigenetic pathways show enhanced efficacy in AML. The combination of DNA methyltransferase inhibitors with histone deacetylase inhibitors has demonstrated synergistic effects in clinical trials. Similarly, combining epigenetic therapies with conventional chemotherapy or targeted agents can overcome resistance mechanisms and improve outcomes.
The monitoring of epigenetic biomarkers during treatment provides valuable information about therapeutic response and resistance development. Changes in methylation patterns and miRNA expression can precede morphological remission, allowing for early assessment of treatment efficacy. This real-time monitoring capability enables treatment modifications and improves patient outcomes. Future research should focus on developing comprehensive epigenetic profiling approaches that integrate multiple biomarker types. The identification of predictive biomarkers that can guide combination therapy selection will be essential for optimizing treatment outcomes. As our understanding of epigenetic regulation in AML continues to evolve, new biomarkers and therapeutic targets will undoubtedly emerge.
Citation: Pablo L (2025). Epigenetic Biomarkers for Precision Medicine in Acute Myeloid Leukemia. J Epigenetics Res. 7:202.
Received: 03-Mar-2025, Manuscript No. EROA-25-38328; Editor assigned: 05-Mar-2025, Pre QC No. EROA-25-38328 (PQ); Reviewed: 19-Mar-2025, QC No. EROA-25-38328; Revised: 26-Mar-2025, Manuscript No. EROA-25-38328 (R); Published: 02-Apr-2025 , DOI: 10.35248/EROA.25.7.202
Copyright: © 2025 Pablo L. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.