Figure 1.

Molecular pathogenesis of Epstein-Barr virus-positive NK/T-cell lymphoma. EBV latent membrane protein-1 (LMP-1) activates the downstream signaling pathways, one of which is the NF-κB pathway. Together with PI3K/Akt pathways, NF-κB leads to the upregulation of survivin, which further inhibits cell apoptosis. Activation of JAK/STAT is associated with the upregulation of EZH2, which results in DNA methylation and gene transcription, and ultimately induces cell proliferation. Both the NF-κB pathway and JAK/STAT pathway upregulates the expression of PD-L1 on the surface of lymphoma cells and they escape from the immune surveillance of activated T cells. The deletion of chromosome 6q silences many tumor suppressor genes, such as PTPRK and PRDMI, which directly result in the activation of JAK/STAT and myc pathways. Moreover, gene mutation including P53, ECSIT, DDX3X are also involved in the oncogenesis of ENKL through the pathways mentioned above.