Risk stratification for survival and transformation into acute myeloid leukemia in patients with myelodysplastic syndrome based on the pathogenicity assessment of TP53 mutations

Introduction. Myelodysplastic syndromes (MDS) are diverse in terms of their appearance, symptoms, survival rate, and progression risk. A TP53 mutation in a patient with MDS indicates a higher risk category, a lower chance of treatment success, a faster progression, and a poorer overall outcome. However, at present, there is insufficient focus on the degree of gene functional deficiency as a result of mutations.

The objective was to develop a system for risk stratification of patients with MDS by assessing the pathogenicity of TP53 mutations.

Methods and materials. We performed a retrospective analysis of TP53 mutations discovered during the 2022 International Working Group for the study of MDS research. The study was done on 2,343 adult patients with MDS without a known deletion in the TP53 gene. Additionally, we reviewed the results of a separate study on the TP53 gene, which involved patients with MDS as well as others with acute myeloid leukemia (AML). This study was conducted at Pavlov University.

Results. Based on the previously established classification algorithm, all patients were divided into three groups: those without a mutation in the TP53 gene, those with a damaging mutation according to the classification system, and those with a neutral genetic variant according to it. There were differences in overall and leukemia-free five-year survival rates between groups of patients with MDS with damaging and neutral variants according to the developed system. Furthermore, a group of patients at the Pavlov University showed a difference in progression-free survival between groups of patients with MDS or AML with damaging and neutral variants according to our classification system.

Conclusion. The novel information system can be used to support medical decision-making in case of detection of variants of unknown significance in the TP53 gene. The universality of the approaches used makes it possible to adapt the system to other genes and pathologies.

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