APR-246 Reveals a Therapeutic Potential Via Triggering Different Cell Death Mechanisms in Diffuse Large B Cell Lymphoma

Background: Diffuse large B cell lymphoma (DLBCL) is the most common lymphoid malignancy and is characterized by its pronounced genetic and clinical heterogeneity. Although the first-line therapy (R-CHOP) improves the curability of patients with DLBCL, nearly 40% remainder ultimately undergo relapsed or refractory disease. Emerging evidence has shown that TP53 mutations correlate with the recurrence and progression of DLBCL. APR-246, also known as PRIMA-1MET, can reactivate the trans-activation of TP53 mutants by facilitating their DNA binding to target genes, making it a promising therapeutic compound for mutated TP53 carcinomas. Although APR-246 in combination with other chemicals has been applied in clinical trials for non-Hodgkin lymphoma (NHL), the efficacy and the underlying molecular mechanisms of APR-246 on DLBCL remain unclear. The arms are to investigate the TP53 mutations and the correlation of mutated TP53 with the prognosis. Furthermore, we evaluated the effect of APR-246 on DLBCL in vitro and in vivo.