Relevance of TP53 mutation in AML

TP53 mutations in AML are considered a disease defining event, making the class of disease incredibly difficult to treat. Prognostication models for these patients should consider factors such as allelic state, frequency, chromosomal abnormalities, and telomere length. The concept of double-hit TP53, which refers to the loss of both copies of TP53, has been found to be significantly detrimental. Bi-allelic loss of TP53 can be defined as having two or more mutations, mutation of one copy and deletion of the wild type copy, or mutation with copy neutral loss of heterozygosity. Although the risk stratification systems still designate patients as having an NPM1 mutated AML if they also have a TP53 mutation, the presence of TP53 mutations in combination with other adverse risk factors is generally considered high-risk disease.