Targeting TP53 Mutations in Myelodysplastic Syndromes

Mutations in TP53 are observed in ∼20% of patients with myelodysplastic syndromes myelodysplastic syndromes: (my-eh-lo-diss-PLASS-tik SIN-dromez) A group of disorders where the bone marrow does not work well, and the bone marrow cells fail to make enough healthy blood cells. Myelo refers to the bone marrow. Dysplastic means abnormal growth or development. People with MDS have low blood cell count for at… (MDS), with increased frequency seen in patients with a complex karyotype and cases of therapy-related MDS therapy-related MDS: see secondary MDS . TP53 mutations represent perhaps the single greatest negative prognostic indicator in MDS. Inferior outcomes are demonstrated with all approved treatment approaches, although hypomethylating agents remain the standard frontline treatment option. Although outcomes with allogeneic hematopoietic stem cell transplant are poor, it remains the only potentially curative therapy. Novel agents are required to improve outcomes in this molecular subgroup, with therapies that directly target the mutant protein and immunotherapies demonstrating greatest potential.