Accurate risk prognostication is central to the management of myelodysplastic syndromes, given the widely heterogeneous clinical outcomes of these bone marrow failure disorders. Over the past decade, the rapidly expanding compendium of molecular lesions in myelodysplastic syndrome (MDS) has offered unprecedented insight into MDS pathobiology. Recently, molecular prognostic models such as the Molecular International Prognostic Scoring System (IPSS-M) have leveraged the wellspring of genetic data to improve upon traditional risk models such as the Revised IPSS (IPSS-R), but also added substantial complexity. In this review, we highlight early MDS prognostic models, the significant advancements in MDS genomics since then, and the recent advent of molecular based prognostic models. We conclude by discussing important opportunities and challenges in the management of MDS as we arrive at the molecular frontier.
