TP53 Mutation Heterogeneity Reveals Distinct Prognoses in Mantle Cell Lymphoma

Background: Mantle cell lymphoma (MCL) is an uncommon and aggressive type of B-cell non-Hodgkin lymphoma, wherein TP53 mutations play a critical role. This study analyzed the effect of different TP53 mutations on the clinical characteristics and prognosis of patients with MCL.

Methods: TP53 sequencing data and clinical and prognostic information were collected from 215 patients with MCL treated at Peking University Third Hospital between August 2017 and December 2022. Furthermore, descriptive and Cox regression analyses were also performed.

Results: Our findings revealed the association between TP53 mutations and higher Ki67 levels (p = 0.008), elevated combined MCL International Prognostic Index (MIPI-c; p = 0.032), and blastoid/pleomorphic subtypes (p = 0.028). Missense mutations (75.6%; G:C > A:T [48.31%]) were the predominant mutation type, occurring within the DNA-binding domain (DBD; 92.41%) and concentrated in exons 5-8 (82.05%). The extent of the impact on prognosis was dependent on the location of the mutations. G245/R273 mutations were associated with the highest risk. Mutations at zinc-binding motifs and DBD were associated with intermediate risk. Non-DBD and non-TP53 mutations were associated with the lowest risks. Three TP53 mutation groups were defined for further analysis. Notably, these groups exhibited significant differences in OS (p = 0.015) and PFS (p = 0.026).

No relevant conflicts of interest to declare.