Identification of genetic abnormalities in MDS patients that may lead to a better diagnosis and treatment strategy of MDS patients | Aplastic Anemia and MDS International Foundation

Identification of genetic abnormalities in MDS patients that may lead to a better diagnosis and treatment strategy of MDS patients

PubMed Abstract: 
Original Publication Date: 
Friday, March 29, 2013

Myelodysplastic syndrome (MDS) represents a group of diseases that can be subdivided into various categories based on clinical, pathological and certain genetic abnormalities.  Subclassification of MDS, especially in terms of predicted risk for a good or bad outcome, is important because it helps doctors to design a treatment plan. New technologies that can search a patient’s complete genetic information for abnormalities in its code (i.e., DNA) have recently revealed additional genetic abnormalities than can be found on a regular basis in blood cells of MDS patients.  This article reviews the clinical importance of these new findings.

Most common were abnormalities in genes called SF3B1, TP53, TET2 and ASXL1.  Currently, it is not known what exactly these types of genetic abnormalities (“somatic mutations”) contribute to MDS development and or progression, and they are not part of the MDS classification systems.  However, some of these genetic abnormalities (in genes called TP53, EZH2, ETV6, RUNX1 and ASXL1), together with other parameters already in use to classify MDS patients, were found to have predictive value in terms of good or bad outcome.  Therefore, including these somatic mutations in the risk classification system may help us to better design patient treatments.

Other mutations were found to predict a response to treatment.  For example: one study showed that the proportion of MDS patients that responded favorable to azacitidine was much higher (nearly twice as high) in the group of patients with a mutation in the TET2 gene in their blood cells compared to the group who did not have this mutation.  Mutations that can predict therapeutic outcome are of importance because it may help doctors design more patient-specific therapies, which are likely to be for successful and with less harmful side effects.

Lastly, mutations found at the time of diagnosis are potentially important indicators of persistence or relapse of disease.  Regular monitoring through e.g. simple blood analysis may help doctors recognize disease progression earlier which may result in earlier interventions with potentially better outcomes.

In summary: new technologies have revealed important common genetic abnormalities in blood cells from MDS patients.  These abnormalities are likely to play in important role in the diagnosis, treatment and monitoring of MDS patients in the near future.

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