Figure 6
From: Anti-apoptotic role and clinical relevance of neurotrophins in diffuse large B-cell lymphomas
Schematic representation of a neurotrophin axis in the biology of DLBCL cells. Neurotrophins (NT) are produced as pro-neurotrophins (pro-NT) and secreted by tumour B cells. Enzymatic cleavage leads to the release of mature NTs in cell microenvironment that realise autocrine/paracrine loops of regulation. In ABC phenotype, activation of the NF-κB pathway enhances the production of NGF. NT signalling (i.e., BDNF/TrkB145) potentiates cell survival pathways and VEGF secretion that are already dependent of constitutively activated pathways in DLBCL cells (PI3K/Akt, MAPK and for ABC subtype the NF-κB pathway). This effect could lead to enhanced resistance to treatment. p75NTR receptor should be involved in cell survival by its interaction with Trk receptor (i.e., full-length TrkB145 or truncated TrkB95) rather than in apoptosis by its sortilin association. Anti-CD20 therapy (i.e., rituximab) inhibits also the constitutively activated survival pathways (like PI3K-Akt) in B tumour cells leading in chemosensitisation to drug-induced apoptosis. Thus Trk pharmacological inhibition (i.e., K252a) can contribute to enhance cell sensitivity to rituximab therapy, notably for relative resistant phenotypes as ABC subtype of DLBCL. The full colour version of this figure is available at British Journal of Cancer online.
