Myelodysplastic syndromes (MDS) are a heterogeneous group of blood disorders characterized by abnormal maturation of the hematopoietic blood cells and premature death of these immature cells leading ultimately to bone marrow failure. Patients with MDS are also at increased risk of developing acute myelogenous and acute lymphoblastic leukemias. Currently available treatments for MDS include serial blood transfusions for refractory anemia, hematopoietic cell growth hormone therapy, and eventually chemotherapy and bone marrow transplantation. However, bone marrow transplants are not an option for some patients due to lack of a matched donor. Additionally, not all patients are eligible for this treatment because of significant risks for long-lasting and severe side effects. New effective treatments are therefore needed.

Mutations in mRNA splicing factors, including SF3B1 and SRSF2, are the most common genetic alterations found in MDS patients. MDS is associated with an inflammatory gene signature suggesting that chronic inflammation contributes to disease pathogenesis. Dr. Suzuki will test whether these mutations sensitize blood cells to necroptosis, an inflammatory form of cell death, resulting in systemic inflammation that contributes to MDS disease propagation. She will also ask whether inhibiting necroptosis can rescue cells with SF3B1 or SRSF2 mutations and allow them to mature normally. If she proves that necroptosis plays a significant role in MDS disease, her work could then be rapidly translated to benefit MDS patients by using necroptosis inhibitor therapies that are currently being tested in the clinic for other diseases. These studies could lead to novel therapeutic options for MDS patients.