Bone Marrow Microenvironment-Induced Chemoprotection in KMT2A Rearranged Pediatric AML Is Overcome by Azacitidine–Panobinostat Combination
Abstract
:Simple Summary
Abstract
1. Introduction
2. Materials and Methods
2.1. Cell Culture, Patient Samples, and Reagents
2.2. Determination of Cell Viability in Multicell Coculture
2.3. Measuring the Effect of Soluble Factors in Chemoprotection with Conditioned Medium
2.4. Adhesion Assay
2.5. Sensitivity Assay
2.6. Xenograft Studies
2.7. Statistical Analysis
3. Results
3.1. Multicell Coculture Exhibits Greater Chemoprotection to AML Cells
3.2. The Chemoprotective Effects of Multicell Coculture on AML Cells Are Dependent on Cell–Cell and Cell–ECM Contact
3.3. Azacitidine and Panobinostat Synergistically Sensitize Leukemic Cells to Cytarabine in Multicell Coculture
3.4. Azacitidine–Panobinostat Treatment Disrupts AML Cell Adhesion
3.5. Epigenetic Drug Treatment Synergistically Sensitizes a Variety of KMT2A Rearranged AML Cells Ex Vivo
3.6. Azacitidine–Panobinostat Combination Mobilizes Leukemia Cells to the Peripheral Blood and Chemosensitizes MV4;11 and NTPL-146 Xenografted Mice
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Lehner, K.M.; Gopalakrishnapillai, A.; Kolb, E.A.; Barwe, S.P. Bone Marrow Microenvironment-Induced Chemoprotection in KMT2A Rearranged Pediatric AML Is Overcome by Azacitidine–Panobinostat Combination. Cancers 2023, 15, 3112. https://doi.org/10.3390/cancers15123112
Lehner KM, Gopalakrishnapillai A, Kolb EA, Barwe SP. Bone Marrow Microenvironment-Induced Chemoprotection in KMT2A Rearranged Pediatric AML Is Overcome by Azacitidine–Panobinostat Combination. Cancers. 2023; 15(12):3112. https://doi.org/10.3390/cancers15123112
Chicago/Turabian StyleLehner, Kara M., Anilkumar Gopalakrishnapillai, Edward Anders Kolb, and Sonali P. Barwe. 2023. "Bone Marrow Microenvironment-Induced Chemoprotection in KMT2A Rearranged Pediatric AML Is Overcome by Azacitidine–Panobinostat Combination" Cancers 15, no. 12: 3112. https://doi.org/10.3390/cancers15123112