Figure 6 from p97 Inhibition Synergistically Enhances Hypomethylating Therapy through Targeting of PLK1 in Acute Myeloid Leukemia
Year: 2026
Type: other
Abstract: CB-5339 in combination with DAC prolongs survival and is well tolerated in an orthotopic AML xenograft model. A, The CB-5339/DAC combination significantly increases overall survival. A disseminated mouse model of AML was generated by injecting MV4-11 cells into the tail veins of NOG mice. Mice were treated with vehicle control, 50 mg/kg CB-5339 daily (oral), 2.5 mg/kg DAC twice weekly (intraperitoneally), or both drugs for the duration of the study. Overall survival for each group was determined by Kaplan–Meier analysis. N = 10 ± SD; * indicates a significant difference from control and single-agent groups, P < 0.005. Median survival values are as follows: vehicle = day 14, CB-5339 = day 19, DAC = day 18, and CB-5339 + DAC = day 22. B, The CB-5339/DAC combination is well tolerated. Mouse weight is shown for all treatment groups. N = 10 ± SD. C, Administration of the CB-5339/DAC combination diminishes CD33+ blasts and PLK1 levels in vivo. Bone marrow specimens were collected from mice in all experimental groups and subjected to IHC analysis to quantify PLK1 and CD33 (leukemia cell marker) levels. Scale bar, 50 μm. D, Quantification of IHC analyses. The number of CD33+ cells were counted in five random fields. For PLK1, signal intensity was quantified using ImageJ software. N = 5 ± SD; * indicates a significant difference from control and single-agent groups, P < 0.005. E, Schematic illustration of the pharmacodynamic synergy of the CB-5339/DAC combination.
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: W7166017417
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