Loss of FBXO9 Enhances Proteasome Activity and Promotes Aggressiveness in Acute Myeloid Leukemia
Abstract
:1. Introduction
2. Results
2.1. FBXO9 Has Low Expression in AML and Expression Correlates to Poor Survival
2.2. Generation of Conditional Knockout of Fbxo9
2.3. Fbxo9 Deletion Leads to Alterations in HSPC Populations
2.4. Deletion of Fbxo9 Leads to an Aggressive and Immature AML Phenotype
2.5. Transplanted Tumors with Reduced Fbxo9 Lead to Rapid Onset of Disease
2.6. Loss of Fbxo9 Leads to Upregulation of Proteins Associated with Tumorigenicity
2.7. Loss of Fbxo9 Correlates with Increased Proteasome Activity
3. Discussion
4. Materials and Methods
4.1. Patient Datasets
4.2. Transgenic Mouse Models
4.3. Flow Cytometry Analysis
4.4. Colony Forming Cell (CFC) Assay
4.5. Histological Staining
4.6. Western Blot Analysis
4.7. RNA Extraction and Quantitative RT-PCR
4.8. TMT Labeling and Mass Spectrometry
4.9. Proteasome Activity Assay
4.10. MTT Assay
4.11. Statistical Analysis
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
References
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Hynes-Smith, R.W.; Swenson, S.A.; Vahle, H.; Wittorf, K.J.; Caplan, M.; Amador, C.; Hyde, R.K.; Buckley, S.M. Loss of FBXO9 Enhances Proteasome Activity and Promotes Aggressiveness in Acute Myeloid Leukemia. Cancers 2019, 11, 1717. https://doi.org/10.3390/cancers11111717
Hynes-Smith RW, Swenson SA, Vahle H, Wittorf KJ, Caplan M, Amador C, Hyde RK, Buckley SM. Loss of FBXO9 Enhances Proteasome Activity and Promotes Aggressiveness in Acute Myeloid Leukemia. Cancers. 2019; 11(11):1717. https://doi.org/10.3390/cancers11111717
Chicago/Turabian StyleHynes-Smith, R. Willow, Samantha A. Swenson, Heather Vahle, Karli J. Wittorf, Mika Caplan, Catalina Amador, R. Katherine Hyde, and Shannon M. Buckley. 2019. "Loss of FBXO9 Enhances Proteasome Activity and Promotes Aggressiveness in Acute Myeloid Leukemia" Cancers 11, no. 11: 1717. https://doi.org/10.3390/cancers11111717