Figure 4 from p97 Inhibition Synergistically Enhances Hypomethylating Therapy through Targeting of PLK1 in Acute Myeloid Leukemia
Year: 2026
Type: other
Abstract: Transcriptomic analyses identify PLK1 as a top early downregulated pharmacodynamic (PD) target of the CB-5339/DAC combination. A, MOLM-13 and MV4-11 cells were treated with 500 nmol/L CB-5339, 1 μmol/L DAC, or both drugs for 6 hours (MV4-11) or 12 hours (MOLM-13) and subjected to RNA sequencing analyses. Time points were selected based on the kinetics of the PD response for each individual cell line to calibrate gene level effects. Heatmaps depict the top PD targets in each cell line. B, qRT-PCR validates the impact of treatment with the CB-5339/DAC combination on PLK1 expression. MV4-11 and MOLM-13 cells were treated with the combination of 250 nmol/L CB-5339, 500 nmol/L DAC for 0, 4, and 8 hours. Relative gene expression levels were quantified by TaqMan qRT-PCR and normalized to 18S rRNA. N = 3 ± SD; * indicates a significant difference from control, P < 0.005. C and D, The CB-5339/DAC combination effectively diminishes PLK1 protein levels. AML cell lines and primary AML specimens were treated with 250 nmol/L CB-5339, 500 nmol/L DAC, or both drugs for 24 hours. The impact of drug treatment on PLK1 protein levels was determined by immunoblotting. Actin documented equal protein loading. E,PLK1 expression is significantly upregulated in patients with AML with adverse-risk features. Patients with AML were stratified by ELN2022 risk group (favorable vs. adverse), and PLK1 expression was quantified. Each dot represents an individual patient. The center line indicates the median and boxes represent the interquartile range. Statistical significance was assessed using a two-sided Wilcoxon rank-sum test (*, P = 0.04).
Authors: Steffan T. Nawrocki, Ning Wang, Claudia M. Espitia, Harley Wu, Claudia Villa Celi, Julian Olea, Paniz Zarand, Homa Dadrastoussi, Hittu Matta, Sruthi Sureshkumar, Madison E. Gamble, Natalie L. Hakim, David Drum, Jack Angeles, Kaijin Wu, Jiang F. Zhong, Xuelian Chen, Alex Duong, Jennifer S. Carew, Kevin R. Kelly
Subfield: Hematology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
OpenAlex ID: W7166092173
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