Synergistic Effects of the RARalpha Agonist Tamibarotene and the Menin Inhibitor Revumenib in Acute Myeloid Leukemia Cells with KMT2A Rearrangement or NPM1 Mutation
Abstract
:Simple Summary
Abstract
1. Introduction
2. Methods
2.1. Cell Lines and Primary AML Cells
2.2. Reagents and Antibodies
2.3. RNA Preparation and RT-qPCR Analysis
2.4. Protein Isolation and Western Blot Analysis
2.5. Flow Cytometry
2.6. Statistics
3. Results
3.1. Determination of Differentiation and Apoptosis Induction after Combination Treatment with Revumenib and Tamibarotene in AML Cell Lines
3.2. Induction of Differentiation and Apoptosis upon Combination Treatment Is Mediated by Restoration of CEBPA and PU.1 Expression and Activation of Caspase-3 and BAX
3.3. Combination of Revumenib and Tamibarotene Demonstrates a Synergistic Reduction in Metabolic Activity
3.4. Transcriptional Effects of Revumenib and Tamibarotene Detected by Quantitative Real-Time PCR
3.5. Effects of Tamibarotene and Revumenib on Differentiation and Apoptosis in Primary AML Cells
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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Patient | Molecular Genetics | Cytogenetics | ELN 2017 Risk Group |
---|---|---|---|
#1 | KMT2A/MLL, DNMT3A, SF3B1 | 46,XY, t(11;19)(q23;p13.3) | high |
#2 | KMT2A/MLLT4 and KMT2A-PTD | 46,XX, t(6;11)(q27;q23) | high |
#3 | n.a. | 46,XX, t(4;11)(X;X) | high |
#4 | n.a. | 46,XY, t(11;19)(q23;p13.1) | high |
#5 | NPM1, BCOR, GATA2, NRAS | 46,XY | intermediate |
#6 | negative | 46,XY, t(9;11)(p21.3;q23) | high |
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Fleischmann, M.; Bechwar, J.; Voigtländer, D.; Fischer, M.; Schnetzke, U.; Hochhaus, A.; Scholl, S. Synergistic Effects of the RARalpha Agonist Tamibarotene and the Menin Inhibitor Revumenib in Acute Myeloid Leukemia Cells with KMT2A Rearrangement or NPM1 Mutation. Cancers 2024, 16, 1311. https://doi.org/10.3390/cancers16071311
Fleischmann M, Bechwar J, Voigtländer D, Fischer M, Schnetzke U, Hochhaus A, Scholl S. Synergistic Effects of the RARalpha Agonist Tamibarotene and the Menin Inhibitor Revumenib in Acute Myeloid Leukemia Cells with KMT2A Rearrangement or NPM1 Mutation. Cancers. 2024; 16(7):1311. https://doi.org/10.3390/cancers16071311
Chicago/Turabian StyleFleischmann, Maximilian, Julia Bechwar, Diana Voigtländer, Mike Fischer, Ulf Schnetzke, Andreas Hochhaus, and Sebastian Scholl. 2024. "Synergistic Effects of the RARalpha Agonist Tamibarotene and the Menin Inhibitor Revumenib in Acute Myeloid Leukemia Cells with KMT2A Rearrangement or NPM1 Mutation" Cancers 16, no. 7: 1311. https://doi.org/10.3390/cancers16071311
APA StyleFleischmann, M., Bechwar, J., Voigtländer, D., Fischer, M., Schnetzke, U., Hochhaus, A., & Scholl, S. (2024). Synergistic Effects of the RARalpha Agonist Tamibarotene and the Menin Inhibitor Revumenib in Acute Myeloid Leukemia Cells with KMT2A Rearrangement or NPM1 Mutation. Cancers, 16(7), 1311. https://doi.org/10.3390/cancers16071311