ROLE OF EPIGENETIC MODIFICATIONS IN THE PATHOGENESIS OF LEUKAEMIA: A NARRATIVE REVIEW

Abstract

Epigenetics refers to heritable changes in gene expression that occur without altering the underlying DNA sequence. Mechanisms such as DNA methylation, histone modifications, and non-coding RNAs regulate key cellular processes, including development, differentiation, and responses to environmental stimuli. Dysregulation of these mechanisms has been strongly linked to the pathogenesis of leukaemia, a diverse group of blood cancers characterised by uncontrolled proliferation of abnormal white blood cells. Aberrant DNA methylation, including hypermethylation of tumour suppressor genes and global hypomethylation, is frequently observed in both acute and chronic leukaemias. Alterations in histone modifications disrupt chromatin structure, influencing transcriptional regulation of genes essential for cell cycle control and apoptosis. In addition, non-coding RNAs such as microRNAs and long non-coding RNAs contribute to leukemogenesis by modulating oncogenic and tumour suppressor pathways. These epigenetic abnormalities are now recognised as active drivers of disease onset and progression, with distinct patterns across leukaemia subtypes, including acute myeloid leukaemia, acute lymphoblastic leukaemia, chronic myeloid leukaemia, and chronic lymphocytic leukaemia. Importantly, epigenetic insights are guiding the development of diagnostic biomarkers and novel therapies, such as DNA methyltransferase and histone deacetylase inhibitors. This narrative review highlights the role of epigenetic modifications in leukaemia pathogenesis.