PROJECT SUMMARY

Around 20% of individuals with myelodysplastic syndromes (MDS) will experience a dangerous bleeding outcome. Platelets are blood cells that assist with preventing and stopping bleeding. While platelet count can play a role, many patients with MDS have normal platelet counts but still develop life-threatening bleeding complications. Our preliminary data shows that there are platelet dysfunction abnormalities in patients with MDS compared to healthy controls and suggests that the genetic MDS mutations may play a role in these outcomes.

My proposal is to determine how the genetics of an individual’s MDS affects platelet function and impacts the risk of developing bleeding complications. We will do this through studying platelet function in MDS patients by testing the ability of their platelets to bind together and release contents, in addition to utilizing cell line and mouse modeling. We will evaluate the megakaryocytes, the cells that make platelets, of MDS patients to understand if their function is similarly affected. Based on preliminary data, we have identified that individuals with MDS with STAG2 mutations seem to have very significant platelet dysfunction and bleeding tendencies. Further studies will help elucidate the risks of bleeding with STAG2 and other mutations in MDS. With these assessments, I will be able to advise on preventative measures and treatments to improve the health of individuals’ with MDS and prevent catastrophic bleeding outcomes.