EPIGENETIC ALTERATIONS IN MYELOID MALIGNANCIES: LINKING CHROMATIN REMODELING TO DISEASE PROGRESSION

Emmanuel Ifeanyi Obeagu; Idi Musimwa

doi:10.22270/ujpr.v11i3.1579

Emmanuel Ifeanyi Obeagu Division of Haematology, Department of Biomedical and Laboratory Science, Africa University, Zimbabwe. Department of Molecular Medicine and Haematology, School of Pathology, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.
Idi Musimwa Division of Haematology, Department of Biomedical and Laboratory Science, Africa University, Zimbabwe.

10.22270/ujpr.v11i3.1579

Keywords:

Chromatin remodeling, disease progression, epigenetic alterations, leukemogenesis, myeloid malignancies

Abstract

Myeloid cancers, such as acute myeloid leukemia (AML), myelodysplastic syndromes (MDS), and myeloproliferative neoplasms (MPNs), develop from the clonal alteration of hematopoietic stem and progenitor cells. Apart from genetic mutations, epigenetic dysregulation has become a key factor in disease onset, advancement, and resistance to treatment. Anomalies in DNA methylation, histone changes, and chromatin rearrangement interfere with normal blood cell differentiation, promote clonal growth, and create diverse malignant cell populations. Alterations in essential epigenetic regulators like DNMT3A, TET2, IDH1/2, ASXL1, and EZH2-collaborate with oncogenic alterations to facilitate leukemogenesis and resistance to treatment. These epigenetic changes act as prognostic indicators and offer targetable weaknesses, such as DNA methyltransferase inhibitors, histone deacetylase inhibitors, and therapies aimed at mutant IDH or EZH2. This review compiles existing information on the epigenetic features of myeloid tumors, emphasizing its importance in disease advancement and treatment strategies.