The presence of significant variability within mutant TP53 acute myeloid leukemia (AML) and myelodysplastic syndrome with excess blast (MDS-EB) prohibits an accurate assessment of prognostic significance for patients. For a study, researchers conducted a comprehensive clinical and molecular investigation of mutant TP53 AML and MDS-EB to analyze the molecular features and establish their influence on survival.
On 2200 AML/MDS-EB specimens, they performed next-generation sequencing to determine the TP53 mutant allelic status (mono- or bi-allelic), the number of TP53 mutations, mutant TP53 clone size, concurrent mutations, cytogenetics, and mutant TP53 molecular minimal residual disease, and the associations of these characteristics with overall survival. TP53 mutations were found in 230 (10.5%) of AML/MDS-EB patients, with a median variant allele frequency of 47%. Bi-allelic mutant TP53 status was found in 174 (76%) of the cases.
In 49 (21%) of the patients, multiple TP53 mutations were discovered. Concurrent mutations were found in 113 (49%) of the patients. There was no significant difference in any of the aforementioned mutant TP53 molecular features between AML and MDS-EB. Patients with mutant TP53 had a dismal prognosis (2-year overall survival, 12.8%); however, no survival difference was seen between AML and MDS-EB. Notably, none of the molecular features were shown to be substantially related to survival in mutant TP53 AML/MDS-EB. Deep sequencing revealed that TP53 mutations remained detectable in the majority of patients even after full remission (73%).
The presence of residual mutant TP53 was not linked to survival. The molecular features and survival of mutant TP53 AML and MDS-EB were identical. As a result, mutant TP53 AML/MDS-EB should be treated as a separate molecular disease entity.