Pan-RAF Inhibition Shows Anti-Leukemic Activity in RAS-Mutant Acute Myeloid Leukemia Cells and Potentiates the Effect of Sorafenib in Cells with FLT3 Mutation
Abstract
:Simple Summary
Abstract
1. Introduction
2. Materials and Methods
2.1. Reagents and Antibodies
2.2. Cell Lines, Co-Culture Experiments, and Pharmacologic Reagents
2.3. Cell Proliferation Assay
2.4. Apoptosis and Cell Viability Assays
2.5. Western Blot Assays
2.6. Reverse Protein Phase Array (RPPA) Analysis
2.7. Statistical Analyses
3. Results
3.1. LY3009120 Induces Anti-Leukemia Effects in AML Cells Harboring NRAS or FLT3 Mutations
3.2. LY3009120 Impacts the RAS-Mediated Signaling Pathway in a Leukemia Cell-Specific Manner
3.3. Combining LY3009120 with Ara-C Overcomes Bone Marrow Stroma-Mediated Chemoresistance
3.4. Concurrent Pan-RAF and FLT3 Inhibition Exerts a Synergistic Antiapoptotic Effect in Sorafenib-Sensitive AML Cell Lines
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Conflicts of Interest
References
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Khoury, J.D.; Tashakori, M.; Yang, H.; Loghavi, S.; Wang, Y.; Wang, J.; Piya, S.; Borthakur, G. Pan-RAF Inhibition Shows Anti-Leukemic Activity in RAS-Mutant Acute Myeloid Leukemia Cells and Potentiates the Effect of Sorafenib in Cells with FLT3 Mutation. Cancers 2020, 12, 3511. https://doi.org/10.3390/cancers12123511
Khoury JD, Tashakori M, Yang H, Loghavi S, Wang Y, Wang J, Piya S, Borthakur G. Pan-RAF Inhibition Shows Anti-Leukemic Activity in RAS-Mutant Acute Myeloid Leukemia Cells and Potentiates the Effect of Sorafenib in Cells with FLT3 Mutation. Cancers. 2020; 12(12):3511. https://doi.org/10.3390/cancers12123511
Chicago/Turabian StyleKhoury, Joseph D., Mehrnoosh Tashakori, Hong Yang, Sanam Loghavi, Ying Wang, Jing Wang, Sujan Piya, and Gautam Borthakur. 2020. "Pan-RAF Inhibition Shows Anti-Leukemic Activity in RAS-Mutant Acute Myeloid Leukemia Cells and Potentiates the Effect of Sorafenib in Cells with FLT3 Mutation" Cancers 12, no. 12: 3511. https://doi.org/10.3390/cancers12123511