Purpose of review: Tumor protein 53 (TP53) protein is involved in fundamental processes of cancer, aging, and DNA repair. Thus, TP53 dysfunction is implicated in malignant processes and remains the most commonly mutated gene in cancer but represents a relatively small proportion in acute myeloid leukemia (AML). Patients with TP53-mutated AML attain inferior responses to therapy resulting in poor overall outcomes.
Recent findings: Traditional treatment approaches with conventional chemotherapy yields suboptimal responses for patients with TP53 mutant AML compared with wildtype TP53. In recent years, there is increasing interest in understanding the role and underlying biology of TP53 mutations in AML with efforts to harness the physiological tumor suppressive function of TP53 protein. Novel combination and targeted therapies may contribute to improved outcomes; however, responses to therapy may be short-lived and ongoing research is indicated to evaluate relapse-risk reduction strategies. These patients may benefit from consideration of enrollment in clinical trials or lower intensity therapy approaches in lieu of intensive chemotherapy.
Summary: Pharmacological treatments targeting the TP53 pathway in addition to novel emerging therapeutics and immunotherapy-based approaches hold promise for treatment of TP53 mutant AML.