Rationale for a Combination Therapy Consisting of MCL1- and MEK-Inhibitors in Acute Myeloid Leukemia
Abstract
:1. Introduction
2. Materials and Methods
2.1. Cell Lines
2.2. Patient Samples
2.3. Cytotoxicity Assays
2.4. Calculation of Combination Index
2.5. Imaging Cytometry
2.6. Measurement of Protein Levels by Western Blot
2.7. Enzyme-Linked Immunosorbent Assay (ELISA)
3. Results
3.1. Synergistic Effects on Cell Viability in AML Cell Lines Treated with the MCL1 Inhibitor S63845 and the MEK Inhibitor Trametinib or the MDM2 Inhibitor HDM201
3.2. Induction of Apoptosis in AML Cell Lines Treated with the MCL1 Inhibitor S63845 and the MEK Inhibitor Trametinib or the MDM2 Inhibitor HDM201
3.3. Varying Sensitivity of Hematological Patient Cells to Treatment with the MCL1 Inhibitor S63845 and the MEK Inhibitor Trametinib
3.4. MCL1 and MEK Protein Levels as Biomarkers for Treatment Response to S63845 and Trametinib
4. Discussion
5. Conclusions
Author Contributions
Funding
Conflicts of Interest
Abbreviations
References
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Seipel, K.; Schmitter, K.; Bacher, U.; Pabst, T. Rationale for a Combination Therapy Consisting of MCL1- and MEK-Inhibitors in Acute Myeloid Leukemia. Cancers 2019, 11, 1779. https://doi.org/10.3390/cancers11111779
Seipel K, Schmitter K, Bacher U, Pabst T. Rationale for a Combination Therapy Consisting of MCL1- and MEK-Inhibitors in Acute Myeloid Leukemia. Cancers. 2019; 11(11):1779. https://doi.org/10.3390/cancers11111779
Chicago/Turabian StyleSeipel, Katja, Karin Schmitter, Ulrike Bacher, and Thomas Pabst. 2019. "Rationale for a Combination Therapy Consisting of MCL1- and MEK-Inhibitors in Acute Myeloid Leukemia" Cancers 11, no. 11: 1779. https://doi.org/10.3390/cancers11111779