Here, we show that DNA damage response by p53 is a central mechanism suppressing the pathogenic cooperation of IKK2ca-enforced canonical NF-κB and impaired differentiation resulting from Blimp1 loss in ABC-DLBCL lymphomagenesis.
Altogether, these results reveal a CD99-miR-9-PRDM1 molecule axis in lymphomagenesis of cHL and suggest that upregulation of CD99 in H/RS cells induces terminal B-cell differentiation, which may provide a novel therapeutic strategies for cHL.
These results demonstrate that BLIMP1 is a bona fide tumor-suppressor gene whose loss contributes to lymphomagenesis by blocking plasma cell differentiation.
Thus, similar to systemic diffuse large B-cell lymphomas, PRDM1 may be a tumor suppressor in some PCNSL and contribute to lymphomagenesis by impairing terminal differentiation.
These findings point to a role for BLIMP1 as a tumor suppressor gene, whose inactivation may contribute to lymphomagenesis by blocking post-GC differentiation of B cells toward plasma cells.