Nuclear BCL10 translocation contributes to lymphoma progression and poor prognosis of peripheral T-cell lymphomas

We evaluated the clinical and biological significance of nuclear BCL10 localization and related signaling in peripheral T-cell lymphomas (PTCLs).

We examined the expression of signaling molecules linked to apoptosis, and AKT/BCL10/BCL3/NF-κB-related signaling molecules in both T-cell lymphoma (TCL) cell lines (SR786 and HuT78). Two TCL cells treated with or without siBCL10 transfection were injected into the mice's flanks in order to evaluate the anti-tumor efficacy of BCL10 knockdown in the xenograft model. We assessed the expression patterns of phosphorylated (p)-AKT/BCL10/BCL3/NF-κB (p65) in tumor cells in 95 patients with PTCLs using immunohistochemical staining.

In both TCL cell lines, siBCL10 inhibited cell viability, arrested cell cycles in the sub-G1 phase, and enhanced the cytotoxicity of doxorubicin and gemcitabine. The siBCL10 upregulated the expression of cleaved PARP, downregulated the expression of nuclear BCL3, NF-κB, and MYC, and reduced the transcriptional activity of NF-κB and NF-κB signaling-related molecules in both TCL cell lines. In both TCL cell lines-derived xenograft mouse models, siBCL10 attenuated tumor growth in TCLs. Patients expressing p-AKT (p = 0.025), nuclear BCL10 (p = 0.001), nuclear BCL3 (p = 0.010), or nuclear NF-κB (p = 0.010) had shorter 5-year overall survival (OS) rates than those not expressing them, respectively. Genetic alterations in T-cell receptor-signaling pathways were more often found in patients with nuclear BCL10 expression. Patients with both nuclear BCL10 expression and RHOA mutation had a significantly worse OS than those without either expression or mutation (p = 0.008).

Nuclear BCL10 translocation contributes to lymphoma progression and poor prognosis in PTCLs by activating NF-κB signaling.