Genetic analyses are beginning to play a larger role in the diagnosis and determination of prognosis for patients with myelodysplastic syndrome (MDS). However, these assays should still be viewed alongside traditional blood and bone marrow test results, since genetic similarities exist between MDS, acute myeloid leukemia (AML), and certain lymphomas, notes Rafael Bejar, MD, PhD.

Certain cytogenetic abnormalities are associated with MDS by World Health Organization classification, such as 5q deletions. Moreover, Bejar notes, certain splicing factor mutations, such as those in SRSF2, SF3B1, and U2AF1, are more enriched in patients with MDS than those with AML and chronic myeloid leukemia (CML). For patients with an uncertain diagnosis, genetic testing can be utilized as a confirmation. Moreover, in patients with a confirmed diagnosis of MDS, specific mutations could help determine prognosis and the aggressiveness of therapy.

At this point, the predictive value of these genetic signatures is best utilized in low-risk patients, believes Rami S. Komrokji, MD, since the integration of molecular data results in the upstaging of approximately 20% to 30% of patients with low-risk MDS. This upstaging is particularly true when using the International Prognostic Scoring System, notes Bejar. The addition of markers such as ferritin, LDH, and mutations can result in a diagnosis of more advanced disease, especially within the intermediate category.

In terms of treatment, these genetic mutations should be viewed with reservation until further clinical data is available, warns Bejar. In some situations, the mutations that predict more aggressive disease may also predict resistance to therapy, suggesting that earlier treatment may not necessarily lead to better outcomes, Bejar states.