Abstract
Significant advances have been achieved in understanding and treating myelodysplastic syndromes (MDS) in the past decade. For the first time, three drugs were approved specifically for this disease. Novel sequencing techniques have expanded our understanding of the molecular basis of MDS. Several clinically significant recurrent gene mutations have been identified. The classification and risk stratification of MDS continues to evolve in light of such advances. However, treatment options remain limited and novel therapeutic strategies are needed. In this review we address key questions for management of MDS. How do we better classify and risk stratify MDS, tailoring treatment accordingly? How do we diagnose and manage the challenging group of patients with MDS/myeloproliferative neoplasms (MPN) overlap? And finally, what is on the horizon for novel therapies?
KEY POINTS
The successful adoption of the International Prognostic Scoring System has prompted the development of several prognostic models aimed at improving risk stratification for myelodysplastic syndromes (MDS). Recent discoveries into the genetic basis of MDS may limit the longevity of these prognostic models that do not include molecular features.
Mutations of several genes in MDS have been shown to carry independent prognostic significance, and tests for these abnormalities are becoming clinically available. Future evidence that somatic mutations can improve the diagnosis and potentially predict response to therapy will drive the demand for genetic testing.
Patients with MDS/MPN have their own distinct disease biology and outcomes than patients with a pure MDS or MPN. We are beginning to understand that diagnostic and treatment approaches will need to be tailored specifically for patients with MDS/MPN and likely their individual subtypes.
Advances in the understanding of molecular genetics, epigenetics, and microRNA patterns may provide insights into the diagnosis, prognosis, and therapies in MDS/MPN. For example, the presence of SF3B1 mutations in 83% of patients with refractory anemia with ring sideroblasts associated with marked thrombocytosis offers the possibility of a synthetic lethal approach by using spliceosome inhibitors.
Several novel agents for treating MDS are being explored. The better understanding of the disease underlying biology with the advent of new molecular technology will hopefully translate into identifying novel therapeutic targets.