ISSN 2997-1036
International Journal of Hematology | Vol. 8, No. 9, September 2017 | pp. 65–72
DOI: 10.46882/2017/IJH/000093
Review Article
Title: Epigenetic alterations and cellular signaling mechanisms in the pathogenesis of myelodysplastic syndromes
Names of Authors: M. A. Bello¹, O. R. Eze²
Authors’ Affiliations: ¹Department of Haematology, Aminu Kano Teaching Hospital, Kano, Nigeria; ²Department of Pathology, University of Benin, Benin City, Nigeria
Abstract: Myelodysplastic syndromes are complex clonal hematopoietic stem cell disorders characterized by ineffective hematopoiesis, cytopenias, and a high propensity for transformation into acute myeloid leukemia. This comprehensive review synthesizes contemporary evidence regarding the epigenetic landscape driving this marrow failure, focusing on somatic mutations within DNA methylation controllers (TET2, DNMT3A, IDH1/2) and histone modification structures (ASXL1). These epigenetic alterations interrupt gene expression patterns, driving hypermethylation within tumor suppressor promoters and inducing proliferative advantages in neoplastic clones. Furthermore, the role of altered RNA splicing machinery (SF3B1, SRSF2) is evaluated relative to megakaryocytic and erythroid dysplasia phenotypes. Concurrently, microenvironmental immune stress cascades within the bone marrow niche, involving elevated tumor necrosis factor-alpha and interleukin-6 signaling, promote accelerated apoptosis of healthy hematopoietic precursors. Understanding these interconnected molecular pathways has led to the successful development of hypomethylating therapies and emerging small-molecule spliceosome inhibitors. This review details structural biomarkers and molecular targets designed to guide risk-stratified therapy and minimize leukemic evolution in high-risk patients.
Keywords: Myelodysplastic syndromes, DNA methylation, epigenetic regulation, spliceosome mutations, marrow niche
Manuscript Timeline: Received: June 18, 2017; Revised: July 24, 2017; Accepted: August 11, 2017; Published: September 15, 2017