EFNB1 level affects drug response in DLBCL cell lines

Abstract

Targeted therapy was a promising therapy for aggressive B-cell lymphoma. However, drug resistance was still an unavoidable problem. Here, we explored the effect of EFNB1 on drug response. Analysis of IC50 data showed that high level of EFNB1 was associated with resistance to most targeted drugs targeting BCR in human DLBCL cell lines. Drug response assay showed that Efnb1 could enhance SRC phosphorylation and increased the sensitivity of cells to SRC inhibitors. Meanwhile, Efnb1 could sensitize cells to most cytotoxic drugs, especially DOX and VCR. Efnb1 could confer cells sensitivity to VCR by enhancing the phosphorylation of Stmn1 at serine 28. Survival analysis revealed that the expression level of genes phosphorylated in Efnb1 cells were associated with poor prognosis of human DLBC. Together, this study revealed that EFNB1 level, as a non-genetic mechanism, greatly affected drug response of targeted drugs and cytotoxic drugs through the phosphorylation network. Our findings would provide important insights into EFNB1-SRC activated B-cell lymphoma and efficacy evaluation.