Fig. 4 | Signal Transduction and Targeted Therapy

Fig. 4

From: Activation of RAS/MAPK pathway confers MCL-1 mediated acquired resistance to BCL-2 inhibitor venetoclax in acute myeloid leukemia

Fig. 4

MAPK pathway activation in VEN-RE cells upregulated MCL-1. a Western blots showing MCL-1 protein levels in parental and VEN-RE MOLM-13 cells treated with 2 mg/mL cycloheximide (CHX) for 0–120 min. b Heatmap showing activation scores for ERK/MAPK signaling in VEN-RE cells based on pathway analysis of the RNA sequencing data. c Western blots showing protein levels of MAPK pathway components in parental (P) and VEN-RE (R) cells. d Western blots showing protein levels of MCL-1 in parental and VEN-RE MOLM-13 cells treated with 20 nM of the MEK inhibitor GDC-0973 (GDC) and 2 mg/mL CHX for 0–120 min. e Fishplots showing clone prevalence at two time points (baseline and relapse) in patient samples 1-7922 and 2-4006. f MCL-1 and BCL-2 expression by immunohistochemistry (IHC) in two paired samples from patients at the time of relapse on VEN clinical trial. Scale bar on the bottom right indicates 20 μm. g Protein expression in two AML patients primary refractory to VEN-based therapy pre- (BL) or post-treatment (no response, NR). h Mechanism of VEN resistance: RAS/MAPK/MCL-1 axis

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