High pyruvate dehydrogenase kinase 4 (PDK4) is associated with R‐CHOP (rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone) resistance in diffuse large B‐cell lymphoma (DLBCL) cells. A, Gene expression detected by RNA sequencing and expression of PDK4 in DLBCL patients. Hierarchical cluster analysis of the top 11 deregulated genes in R‐CHOP‐sensitive patients (n = 4) and R‐CHOP‐resistant patients (n = 3). Upregulated genes are shown in red and downregulated genes are shown in blue. B, PDK4 mRNA expression between germinal‐center B‐cell‐like (GCB)‐DLBCL (n = 30) and activated B‐cell‐like (ABC)‐DLCBL (n = 26) subtypes among 56 cases in the DLBCL cohort. *P < .05. C, D, Real‐time quantitative PCR analysis of PDK4 mRNA and MS4A1 mRNA expression in R‐CHOP‐sensitive patients (n = 37) and R‐CHOP‐resistant patients (n = 19) with DLBCL. E, Pearson correlation analysis for PDK4 and MS4A1 expression in 56 cases in the DLBCL cohort (Pearson r = −0.41, P = .0021, with F test). F, G, Assessment of mRNA and protein levels of PDK4 in R‐CHOP‐resistant DLBCL cell line SU‐DHL‐2/R and rituximab‐resistant DLBCL cell line OCI‐ly8/R, as well as their parental cell lines. H, Representative images of immunofluorescence analysis for PDK4 (red) and CD20 (green) protein expression in SU‐DHL‐2/R and parental cells. Scale bar, 15 μm