Proteomics of primary AML patient samples reveal upregulation of FLT3 and MAPK signaling in venetoclax-azacitidine–resistant samples. (A) Experimental setup of the proteomic experiments conducted with primary patient samples. FLT3 wild-type samples (n = 6) were divided into 2 groups according to Bliss scores achieved by venetoclax-azacitidine in the drug screening approach (high responders [n = 2] vs low responders [n = 4]). Cells were sorted for high CD34 and moderate CD45 expression, and whole proteome was examined by mass spectrometry and compared. (B) Maximum venetoclax-azacitidine Bliss scores of FLT3 wild-type patient samples analyzed by proteomics. Bliss >5 was defined as high response. (C) Normalized enrichment score (NES) plot for FLT3 (left) and MAPK (right) signaling in AML samples with high ex vivo response vs low response to venetoclax-azacitidine. (D) Heat map of FLT3 signaling–associated (top) and MAPK signaling–associated (bottom) proteins differentially expressed in AML samples with high ex vivo response vs low response to venetoclax-azacitidine.