Unlike its Paralog LEDGF/p75, HRP-2 Is Dispensable for MLL-R Leukemogenesis but Important for Leukemic Cell Survival
Abstract
:1. Introduction
2. Materials and Methods
2.1. Viral Vector Transductions and Generation of Stable Cell Lines
2.2. Protein Purification
2.3. AlphaScreen Assay
2.4. Co-Immunoprecipitation (IP)
2.5. Peptide Synthesis
2.6. NMR Spectroscopy
2.7. HRP-2 Knockout Mouse Mode
2.8. Clonogenic Growth In Vitro
2.9. RNA-Sequencing and Bioinformatics
2.10. Statistical Analysis
3. Results
3.1. HRP-2 Interacts with MLL in the Absence of Menin
3.2. HRP-2 and LEDGF/p75 Interact with MLL through a Conserved Interface with Similar Affinities
3.3. Systemic HRP-2 Depletion in Mice Leads to Increased Postnatal Mortality and Decreased In Vitro Colony Formation of Hematopoietic Stem Cells
3.4. HRP-2 Depletion Impairs the Clonogenic Growth of Both Human and Mouse Leukemic Cell Lines Independently of MLL Fusions
3.5. HRP-2 Overexpression Rescues MLL-r Clonogenic Growth in LEDGF/p75-Depleted Cells
3.6. HRP-2 Is Dispensable for the Initiation of MLL-r Leukemia
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Number (%) of Mice | |||
---|---|---|---|
Age | HRP-2+/+ | HRP-2+/− | HRP-2−/− |
1 day | 36 (23.2) | 88 (56.7) | 31 (20.0) |
6–8 weeks | 31 (29.5) | 64 (61.0) | 10 (9.5) |
Expected values | 25% | 50% | 25% |
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Van Belle, S.; El Ashkar, S.; Čermáková, K.; Matthijssens, F.; Goossens, S.; Canella, A.; Hodges, C.H.; Christ, F.; De Rijck, J.; Van Vlierberghe, P.; et al. Unlike its Paralog LEDGF/p75, HRP-2 Is Dispensable for MLL-R Leukemogenesis but Important for Leukemic Cell Survival. Cells 2021, 10, 192. https://doi.org/10.3390/cells10010192
Van Belle S, El Ashkar S, Čermáková K, Matthijssens F, Goossens S, Canella A, Hodges CH, Christ F, De Rijck J, Van Vlierberghe P, et al. Unlike its Paralog LEDGF/p75, HRP-2 Is Dispensable for MLL-R Leukemogenesis but Important for Leukemic Cell Survival. Cells. 2021; 10(1):192. https://doi.org/10.3390/cells10010192
Chicago/Turabian StyleVan Belle, Siska, Sara El Ashkar, Kateřina Čermáková, Filip Matthijssens, Steven Goossens, Alessandro Canella, Courtney H. Hodges, Frauke Christ, Jan De Rijck, Pieter Van Vlierberghe, and et al. 2021. "Unlike its Paralog LEDGF/p75, HRP-2 Is Dispensable for MLL-R Leukemogenesis but Important for Leukemic Cell Survival" Cells 10, no. 1: 192. https://doi.org/10.3390/cells10010192
APA StyleVan Belle, S., El Ashkar, S., Čermáková, K., Matthijssens, F., Goossens, S., Canella, A., Hodges, C. H., Christ, F., De Rijck, J., Van Vlierberghe, P., Veverka, V., & Debyser, Z. (2021). Unlike its Paralog LEDGF/p75, HRP-2 Is Dispensable for MLL-R Leukemogenesis but Important for Leukemic Cell Survival. Cells, 10(1), 192. https://doi.org/10.3390/cells10010192