Stintzing, Sebastian; Kemmerling, Ralf; Kiesslich, Tobias; Alinger, Beate; Ocker, Matthias; Neureiter, Daniel
Myelodysplastic Syndrome and Histone Deacetylase Inhibitors: ``To Be or Not to Be Acetylated''?
In: Journal of Biomedicine and Biotechnology, Vol. 2011, 214143
Myelodysplastic syndrome (MDS) represents a heterogeneous group of diseases with clonal proliferation, bone marrow failure and increasing risk of transformation into an acute myeloid leukaemia. Structured guidelines are developed for selective therapy based on prognostic subgroups, age, and performance status. Although many driving forces of disease phenotype and biology are described, the complete and possibly interacting pathogenetic pathways still remain unclear. Epigenetic investigations of cancer and haematologic diseases like MDS give new insights into the pathogenesis of this complex disease. Modifications of DNA or histones via methylation or acetylation lead to gene silencing and altered physiology relevant for MDS. First clinical trials give evidence that patients with MDS could benefit from epigenetic treatment with, for example, DNA methyl transferase inhibitors (DNMTi) or histone deacetylase inhibitors (HDACi). Nevertheless, many issues of HDACi remain incompletely understood and pose clinical and translational challenges. In this paper, major aspects of MDS, MDS-associated epigenetics and the potential use of HDACi are discussed.