Figure 1 from p97 Inhibition Synergistically Enhances Hypomethylating Therapy through Targeting of PLK1 in Acute Myeloid Leukemia
Year: 2026
Type: other
Abstract: CB-5339 reduces AML cell viability in cell lines and primary cells. A, A panel of established AML cell lines with diverse genetic features and normal CD34+ bone marrow cells were treated with the indicated concentrations of CB-5339 for 72 hours. Cell viability was determined by MTT assay. N = 3 ± SD. IC50 values for each cell line are indicated. B, Primary AML cells from patients (N = 4) were treated with the indicated concentration of CB-5339 for 72 hours. Cell viability was determined by MTT assay. N = 3 ± SD. Characteristics of primary AML specimens are indicated. C, CB-5339 induces time-dependent accumulation of ubiquitin-conjugated proteins. Primary AML cells from patient #1, #2, and #3 were treated with 300 nmol/L CB-5339 for the indicated times. The effects of drug treatment on ubiquitin-conjugated protein levels were determined by immunoblotting. GAPDH documented equal protein loading. D, CB-5339 induces dose-dependent apoptosis. A panel of seven established AML cell lines was treated with the indicated concentrations of CB-5339 for 48 hours. Drug-induced apoptosis was quantified by PI/FACS analysis. N = 3 ± SD. E, CB-5339 triggers time-dependent DNA damage and ER stress. MOLM-13 cells were treated with increasing concentrations of CB-5339 (0–2,500 nmol/L) for 3, 5, or 12 hours. Western blotting was performed to assess the impact of drug treatment on the indicated protein levels of γ-H2AX, cleaved caspase-3, PARP, XBP1s, CHOP, and ATF-6. Arrows denote cleaved PARP and ATF6. GAPDH was used as a loading control.
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: W7166103537
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