FIG. 1.

Illustration of cross-communication network of BCR, PI3K, and NF-κB signaling pathways that harbor effective therapeutic targets in lymphoma. BCR signaling, PI3K/AKT/mTOR signaling, and NF-κB signaling are independent but interconnected and may form complex crosstalk network. One pathway may act as upstream or downstream of other pathways and some molecular targets function as key points and players involved in several pathways. These key molecules have been shown promise to be a good therapeutic target for effective treatment in lymphoid malignancies. (A) Tonic BCR signaling pathway and PI3K/AKT/mTOR signaling pathway; (B) chronic active BCR signaling; (C) canonical NF-κB signaling pathway; (D) noncanonical NF-κB signaling pathway. The arrows indicate direction of activating signaling steps; the light-colored bars indicate inhibitory signaling steps; the black bars show inhibition from therapeutic agents toward targets. BAFF-R, B-cell activating factor receptor; BCR, B-cell receptor; BTK, Bruton’s tyrosine kinase; CARD11, caspase recruitment domain family, member 11; IKK, IκB kinase; MALT1, mucosa-associated lymphoid tissue lymphoma translocation protein 1; NEMO, NF-κB essential modifier; NIK, NF-κB-inducing kinase; mTOR, mammalian target of rapamycin; PI3K, phosphatidylinositol 3 kinase; TCR, T-cell receptor; TLRs, Toll-like receptors; TNFR, tumor necrosis factor receptor.