# TP53-mutated myelodysplastic syndromes and acute myeloid leukemia: a comprehensive overview of targeted approaches

## TL;DR

This paper reviews the challenges and treatment options for blood cancers with TP53 mutations, which are hard to treat and have poor outcomes.

## Contribution

The paper provides a comprehensive overview of targeted therapies and clinical trials for TP53-mutated AML and MDS.

## Key findings

- TP53 mutations are linked to poor prognosis and resistance to standard treatments in AML and MDS.
- Current therapies like hypomethylating agents and venetoclax offer limited benefits.
- New strategies targeting mutant p53 or synthetic lethal pathways are being explored.

## Abstract

TP53-mutated acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS) represent a biologically and clinically distinct subset of myeloid malignancies characterized by poor prognosis, resistance to standard therapies, and high rates of relapse. TP53 mutations, particularly biallelic are frequently associated with complex karyotypes and confer profound chemoresistance. Although hypomethylating agents and venetoclax-based combinations provide modest benefit, durable remissions remain rare. Novel therapeutic strategies targeting mutant p53, restoring wild-type function, or exploiting synthetic lethal pathways are under active investigation. This review aims to summarize current knowledge on the biology of TP53, prognostic implications, and therapeutic landscape of TP53-mutated AML/MDS, ongoing and past clinical trials in TP53-mutated AML/MDS patients, emphasizing the need for precision-guided, multimodal approaches to improve outcomes in this high-risk group.