MYC and MYC-controlled genes are effectively targeted by HSP90 inhibition through PU-H71. (A) GSEA enrichment analyses show MYC gene signature was downregulated by 0.5 µM PU-H71 treatment in ibrutinib-resistant MAVER cells. FDR and P values are indicated. (B) Heat map representation of top-ranked MYC signature genes that are downregulated by PU-H71 in comparison with DMSO or ibrutinib. Biological triplicate experiments, represented by 3 columns for each condition, were shown. (C) Summary of the transcriptomic response of JEKO and MAVER cells to ibrutinib and PU-H71 across multiple oncogenic gene signatures. (D) Protein levels of MYC in 4 MCL cell lines were also downregulated at 24 hours by increasing concentrations of PU-H71. GAPDH, loading control. (E) 50% infective dose values of PU-H71 is significantly decreased (P < .05) in 4 MCL cell lines after MYC knock down. One-way analysis of variance test was used for statistical analysis.