Targeting p53 in MDS

Introduction Myelodysplastic syndromes (MDS) represent a heterogeneous group of malignant stem cell neoplasms hallmarked by ineffective hematopoiesis and risk of leukemic transformation. Advancements in genomic techniques such as next generation sequencing (NGS) have dramatically enhanced our knowledge of the underlying genetic alterations in MDS. Of all somatic mutations identified in MDS, TP53 mutations are associated with the most inferior outcomes across independent studies with a median OS of 6–12 months.1,2Additionally, TP53 mutations predict for inferior OS to hypomethylating agents, as well as allogeneic stem cell transplantation, which are the only disease modifying therapies.3–7 Together, these data highlight the profound negative connotation of TP53 mutation in MDS and the urgent need for effective, biologically rational, targeted therapies.