Unravelling the Epigenome of Myelodysplastic Syndrome: Diagnosis, Prognosis, and Response to Therapy

Simple Summary Myelodysplastic syndrome (MDS) is a type of blood cancer that mostly affects older individuals. Invasive tests to obtain bone samples are used to diagnose MDS and many patients do not respond to therapy or stop responding to therapy in the short-term. Less invasive tests to help diagnose, prognosticate, and predict response of patients is a felt need. Factors that influence gene expression without changing the DNA sequence (epigenetic modifiers) such as DNA methylation, micro-RNAs and long-coding RNAs play an important role in MDS, are potential biomarkers and may also serve as targets for therapy. Abstract Myelodysplastic syndrome (MDS) is a malignancy that disrupts normal blood cell production and commonly affects our ageing population. MDS patients are diagnosed using an invasive bone marrow biopsy and high-risk MDS patients are treated with hypomethylating agents (HMAs) such as decitabine and azacytidine. However, these therapies are only effective in 50% of patients, and many develop resistance to therapy, often resulting in bone marrow failure or leukemic transformation. Therefore, there is a strong need for less invasive, diagnostic tests for MDS, novel markers that can predict response to therapy and/or patient prognosis to aid treatment stratification, as well as new and effective therapeutics to enhance patient quality of life and survival. Epigenetic modifiers such as DNA methylation, long non-coding RNAs (lncRNAs) and micro-RNAs (miRNAs) are perturbed in MDS blasts and the bone marrow micro-environment, influencing disease progression and response to therapy. This review focusses on the potential utility of epigenetic modifiers in aiding diagnosis, prognosis, and predicting treatment response in MDS, and touches on the need for extensive and collaborative research using single-cell technologies and multi-omics to test the clinical utility of epigenetic markers for MDS patients in the future.