The myelodysplastic syndromes are now recognized as one of the most common blood cancers, affecting >30,000 patients per year in the United States. Although 3 drugs were approved for MDS between the years 2004 – 2006 (azacitidine, decitabine, and lenalidomide), none of these are curative. In addition, no new drugs have been approved in the last 8 years. Newer laboratory and genomic research may help to shift this paradigm. Scientists are now working to better understand how patients get MDS, how we can improve diagnostic accuracy, and how we can refine our prognostic models, which may eventually lead to improved treatments and outcomes.
-Since 2007, new sequencing techniques have led to the discovery of recurrently mutated genes in MDS, which have improved our understanding of how the disease develops and changes over time.
-Chromosomal abnormalities are useful for both diagnosis and prognosis in MDS patients. A classic example is that patients with chromosome 5q deletions are more likely to respond to lenalidomide.
-High-resolution genome-wide techniques can detect chromosomal abnormalities that are not found using conventional techniques. This has led to the discovery of individual genes that are important to the development of MDS. It has also led to the understanding that epigenetic regulation and RNA splicing are the key molecular pathways that are dysregulated in MDS.
-The presence of mutations may ultimately serve as a marker to monitor for disease progression in individual patients.
-Establishing a diagnosis of MDS can be complex. Better understanding of the molecular basis of MDS will help to distinguish MDS from benign causes of low blood counts and can help patients who need treatment be identified earlier in the course of their disease.
-Determining prognosis for patients with MDS is important, both in setting expectations for patients as well as helping clinicians to formulate treatment plans. The Revised International Prognostic Scoring System (IPSS-R) is the most current accepted model that is utilized, and it incorporates chromosomal abnormalities, bone marrow blasts, cytopenias, age, and additional factors to determine prognosis. However, it does not take into account molecular abnormalities. Incorporating this information will help to improve current prognostic models.
-Predicting response to treatment in patients with MDS can be challenging. Few useful biomarkers are currently available, such as serum EPO level and the presence of del (5q). No specific chromosome or molecular markers have consistently predicted response to azacitidine or decitabine.
-There are several novel agents and combinations of agents that are currently being tested in clinical trials for patients with MDS.
-No new drugs have been approved for MDS by the US Food and Drug Administration since 2006. Current available therapies can be efficacious but are generally not curative.
-Some of the challenges in developing new treatments are the complexity and heterogeneity of MDS as a disease.
-The availability of molecular tests has advanced our knowledge of MDS and will be useful in determining better diagnostic and therapeutic approaches to deal with the disease moving forward.