Distinct patterns of B-cell receptor signaling in non-Hodgkin lymphomas identified by single-cell profiling

摘要: Kinases downstream of B-cell antigen receptor (BCR) represent attractive targets for therapy in non-Hodgkin lymphoma (NHL). As clinical responses vary, improved knowledge regarding activation and regulation BCR signaling individual patients is needed. Here, using phosphospecific flow cytometry to obtain malignant profiles from 95 representing 4 types NHL revealed a striking contrast between chronic lymphocytic leukemia (CLL) mantle cell (MCL) tumors. Lymphoma cells diffuse large had high basal phosphorylation levels most measured nodes, whereas follicular represented the opposite pattern with no or very low levels. MCL showed interpatient variability levels, elevated phosphorylated forms AKT, extracellular signal-regulated kinase, p38, STAT1, STAT5 were associated poor outcome. CLL tumors BCR-signaling nodes (Src family tyrosine spleen kinase [SYK], phospholipase Cgamma), but alpha-BCR-induced signaling. This contrasted tumors, where was variable, significantly potentiated as compared other types. Overexpression CD79B, combined gating strategy whereby output directly quantified per function CD79B confirmed direct relationship surface immunoglobulin M (IgM), IgM-induced Furthermore, strength variable across patient samples correlated subunit expression, inversely susceptibility Bruton (BTK) SYK inhibitors MCL. These differences might relate BCR-pathway inhibitors.