Gene regulation and suppression of type I interferon signaling by STAT3 in diffuse large B cell lymphoma

Abstract

Significance We demonstrate that STAT3 is a critical transcriptional regulator of the activated B cell–like subtype of diffuse large B cell lymphoma (ABC DLBCL), the most common, aggressive, non-Hodgkin lymphoma. By genome-wide assessment, we have identified target genes of STAT3. Gene regulation by STAT3 in ABC DLBCL accentuates survival signaling pathways while dampening the lethal type I interferon pathway. Knowledge of these STAT3-regulated genes has led to our demonstration that a small-molecule inhibitor in the JAK1-STAT3 signaling pathway synergizes with the type I interferon inducer lenalidomide, suggesting a new therapeutic strategy for ABC DLBCL, a subtype that is particularly difficult to treat and has poor prognosis.