TP53 mutations occur in 9.0% of MDS (COSMIC). TP53 mutations are most often observed in patients with advanced disease or whose tumors harbor a complex karyotype, chromosome 17 abnormalities, chromosome 5 deletions, or chromosome 7 deletions (Cazzola, Della Porta, and Malcovati 2013). The role of TP53 mutations in MDS is not yet well understood. These mutations are found spread throughout the gene.

TP53 mutations are a prognostic biomarker for decreased overall survival and have been associated with a higher likelihood of transformation to AML (Bejar et al. 2011; Cazzola, Della Porta, and Malcovati 2013; NCCN 2014). In addition, Bejar et al. (2014) observed that TP53 mutations predict shorter overall survival following hematopoietic stem cell transplantation. In MDS with chromosome 5 deletions, TP53 mutations have been associated with poor response to the drug lenalidomide, a thalidomide analog (Cazzola, Della Porta, and Malcovati 2013).​