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Letters to the Editor
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Figure 2. The BETi CPI203 synergizes with IRAKi in activated B-cell - diffuse large B cell lymphoma mediated by the inhibition of NF-κB downstream pathways. (A) Enrichment plots from gene set enrichment analysis (GSEA) analysis comparing IRAKi single agent vs. IRAKi-CPI203 combo in the 3 cell lines treated for 6 hours (Affymetrix HG-U219; GSEA), showing a significant improvement of NF-κB signature decrease by the addition of CPI203 to IRAKi. (B) Quantitative reverse transcriptase polymerare chain reaction (RQ-PRC) analysis of NF-κB downstream genes in the three cell lines exposed to IRAKi, CPI203 or CPI203-IRAKi combo as before. (*P=0.01; **P<0.001). (C) CPI203-IRAKi combination led to intracellular accumulation of IκB, and subsequent downregulation of IRAK1, MYC, CD44, MARCKS and MCL-1 proteins in activated B-cell - diffuse large B cell lymphoma (ABC-DLBCL) cells with MYD88L265P. (D) OCI-Ly3, OCI-Ly10, HBL-1 cells were exposed for 24 hours to 0.1-0.5 mM CPI203 and/or 50-500 mM IRAKi. Cytotoxicity was evaluated by MTT assay and combination index (CI) was determined using the Calcusyn software. Shown are the cytotoxicity and the mean CI value calculated for cell treatment with 0.5 mM CPI203 and 50 mM IRAKi. (E) The drug com- bination led to a synergistic antitumoral effect in vitro in these 3 cell lines, inducing a median 36% increase in apoptosis rate when compared to single agent treatments (*P<0.04).
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