Anthracycline and antimetabolite, trigger distinct resistance mechanisms in TP53mut AML

Abstract

Acute myeloid leukemia (AML) is a highly heterogeneous and extremely aggressive form of blood cancer. Despite recent advances, AML continues to be a challenging disease to treat; the overall prognosis and response to therapy are strongly influenced by karyotypic and molecular alterations [ 1 ]. Mutations of the Tp53 gene ( TP53 mut ) are among the most common alterations found in human malignancies, affecting 5–20% of de novo AML and more frequently (up to 37%) observed in patients with therapy-related AML [ 1 , 2 ]. The TP53 mut AML has also been associated with a lower response to conventional chemotherapies, high relapse, and inferior overall survival [ 2 , 3 , 4 ]. Since 2017, the Food and Drug Administration (FDA) has approved several new drugs for AML [ 1 ], but treating TP53 muts AML remains a formidable challenge.