The epigenetic revolution in hematology: from benchside breakthroughs to clinical transformations
Mahdis Abdar Esfahani, Nazli Servatian, Ali Jihad Hemid Al-Athari, Elaf Salah Mehdi Khafaja, Hamideh Rahmani Seraji, Hamed Soleimani Samarkhazan
Abstract
The field of hematology has experienced a substantial evolution with the acknowledgment of epigenetic processes as essential factors in the development of hematological malignancies. This review article examines the influence of epigenetic alterations, namely DNA methylation and histone modifications, on the onset and advancement of conditions such as acute myeloid leukemia and myelodysplastic syndromes. We discuss how these epigenetic modifications lead to the deregulation of gene expression, eventually promoting leukemogenesis. The emergence of epigenetic therapies, such as DNA methyltransferase inhibitors (e.g., azacitidine and decitabine), histone deacetylase inhibitors (e.g., vorinostat and romidepsin), and enhancer of zeste homologue 2 inhibitors (e.g., tazmetostat), demonstrates the potential to reverse aberrant epigenetic modifications and restoring normal cellular functions. Moreover, we highlight innovative therapeutic approaches, including combination therapies and CRISPR-based epigenetic editing tools, which are influencing the future of treatment for hematological malignancies. Despite promising results, challenges such as off-target effects, drug resistance, and the need for personalized approaches remain significant barriers to effective treatment. We emphasize that further study is required to improve delivery systems, comprehend resistance mechanisms and develop precision medicine strategies that can tailor therapies to individual patient profiles. By integrating benchside discoveries with clinical applications, this review aims to illuminate the transformative potential of epigenetic therapies in improving patient outcomes in hematology. Epigenetic dysregulation including aberrant DNA methylation, histone modifications, and chromatin remodeling is a key driver in the initiation and progression of hematologic malignancies. Therapeutic strategies targeting these epigenetic mechanisms aim to restore normal gene expression, induce differentiation, and overcome drug resistance.