Prognostic Impact of MYD88 and TP53 Mutations in Diffuse Large B Cell Lymphoma
Authors: Hameed Ebid Osama Abd El , El Arab Lobna R Ezz , Saad Amr S , Din Mai Ezz El , Mostafa Nermeen , Swellam Menha 
Published: November 2024

Abstract

Background
Diffuse large B cell lymphoma (DLBCL) is the most common subtype of lymphoma, It is a highly heterogeneous lymphoid neoplasm, with variations in gene expression profiles and genetic alterations, MYD88 and TP53 genes are common to be expressed and mutated in DLBCL patients with controversy regarding their role in prognosis and survival. This study aims to determine the predictive and prognostic role of MYD88 and TP53 genes mutation in DLBCL.

Methods
A prospective cohort study was conducted on patients who were diagnosed with DLBCL in Ain Shams university hospital, the primary objective was to detect the sensitivity and the specificity of MYD88 and TP53 genes expression for prognosis and detection of DLBCL patients. Secondary objectives were to measure ORR, 2 year PFS, and OS in relation to MYD88 and TP53 genes expression profile by detection of their expression profile using real time PCR approach.

Results
A total 50 DLBCL patients and 30 healthy individuals were included to assess sensitivity and specificity of MYD88 and TP53 genetic mutations in DLBCL prognosis. MYD88 and TP53 gene mutations were more sensitive, specific and accurate in predicting overall mortality (MYD88 sensitivity 95.1%, specificity 87.5%, prognostic accuracy 93.9%, P value &lt;0.001, AUCROC 0.91, while TP53 sensitivity 82.9%, specificity 87.5%, prognostic accuracy 83.7%, P value 0.002, AUCROC 0.85) and disease progression (MYD88 sensitivity 92.5%, specificity 88.9%, prognostic accuracy 90.7%, P value &lt;0.001, AUCROC 0.85, while TP53 sensitivity 94.3%, specificity 64.3%, prognostic accuracy 85.7%, P value 0.001, AUCROC 0.84) in comparison with international prognostic index(OS Sensitivity 70.7%, and specificity 75%, prognostic accuracy 71.4%, P value 0.011, AUCROC 0.79, while for progression, sensitivity is 79.2%, and specificity is 100%, prognostic accuracy 79.6%, P value 0.021, AUCROC 0.73). Mutant MYD88 and TP53 showed their prognostic importance for worse objective response rates and survival outcomes. Both mutant MYD88 and TP53 were associated with worse ORR (p- value=0.001). There was a significant statistical difference for both MYD88 and TP53 as regard 2 year PFS rate (Mutant 25% Vs 100% wild MYD88 P &lt; 0.001, and Mutant TP53 62% Vs 97% wild TP53 P &lt; 0.001), 2 year OS rate (Mutant MYD88 33% Vs wild MYD88 100% P &lt; 0.001,and MutantTP53 70% Vs wild TP53 96% P &lt; 0.001).

Conclusion
Both mutant MYD88 and TP53 can be used in predicting disease progression, and overall mortality. They showed their prognostic importance for inferior survival outcomes. mutations were associated with a significant worse 2 year OS and PFS rates and also they were correlated with poor objective response rate to treatment. The current study shows that the incorporation of the mutational status of MYD88 and TP53 (especially MYD88) into a clinical-biochemical risk score as the IPI is feasible. This encourages for more studies to test the utility of these gene mutations in prognosis of DLBCL.