Children's Hospital, Immune Disease Institute, Harvard Medical School, Boston, MA 02115, USA.
Cancer Cell. 2010 Dec 14;18(6):580-9. doi: 10.1016/j.ccr.2010.11.024.
Diffuse large B cell lymphoma (DLBCL) comprises disease entities with distinct genetic profiles, including germinal center B cell (GCB)-like and activated B cell (ABC)-like DLBCLs. Major differences between these two subtypes include genetic aberrations leading to constitutive NF-κB activation and interference with terminal B cell differentiation through BLIMP1 inactivation, observed in ABC- but not GCB-DLBCL. Using conditional gain-of-function and/or loss-of-function mutagenesis in the mouse, we show that constitutive activation of the canonical NF-κB pathway cooperates with disruption of BLIMP1 in the development of a lymphoma that resembles human ABC-DLBCL. Our work suggests that both NF-κB signaling, as an oncogenic event, and BLIMP1, as a tumor suppressor, play causal roles in the pathogenesis of ABC-DLBCL.
弥漫性大 B 细胞淋巴瘤 (DLBCL) 包括具有不同遗传特征的疾病实体，包括生发中心 B 细胞 (GCB) 样和激活 B 细胞 (ABC) 样 DLBCL。这两种亚型之间的主要区别包括导致 NF-κB 持续激活的遗传异常，以及通过 BLIMP1 失活干扰终末 B 细胞分化，这在 ABC-DLBCL 中观察到，但在 GCB-DLBCL 中未观察到。我们使用小鼠的条件性获得功能和/或丧失功能诱变，表明经典 NF-κB 通路的持续激活与 BLIMP1 的破坏在发展类似于人类 ABC-DLBCL 的淋巴瘤中协同作用。我们的工作表明，NF-κB 信号传导作为致癌事件，以及 BLIMP1 作为肿瘤抑制因子，在 ABC-DLBCL 的发病机制中都发挥着因果作用。
