TLR Signaling Is Activated in Lymph Node-Resident CLL Cells and Is Only Partially Inhibited by Ibrutinib.

ABSTRACT: Chronic lymphocytic leukemia (CLL) is a malignancy of mature B cells driven by B-cell receptor (BCR) signaling and activated primarily in the lymph node. The Bruton's tyrosine kinase (BTK) inhibitor ibrutinib effectively inhibits BCR-dependent proliferation and survival signals and has emerged as a breakthrough therapy for CLL. However, complete remissions are uncommon and are achieved only after years of continuous therapy. We hypothesized that other signaling pathways that sustain CLL cell survival are only partially inhibited by ibrutinib. In normal B cells, Toll-like receptor (TLR) signaling cooperates with BCR signaling to activate prosurvival NF-κB. Here, we show that an experimentally validated gene signature of TLR activation is overexpressed in lymph node-resident CLL cells compar

SUBMITTER: Dadashian EL 

PROVIDER: S-EPMC6342512 | biostudies-literature | 2019 Jan

REPOSITORIES: biostudies-literature