Hematopoietic Stem Cell (HSC)-Independent Progenitors Are Susceptible to Mll-Af9-Induced Leukemic Transformation
Abstract
:Simple Summary
Abstract
1. Introduction
2. Materials and Methods
2.1. Mouse Strains
2.2. Polymerase Chain Reaction (PCR) for Mll-Af9 Detection and Sequencing
2.3. Flow Cytometry and Hematological Analysis
2.4. Primary and Secondary Transplants
2.5. Histological Analysis
2.6. Fluorescence-Activated Cell Sorting (FACS) for the Isolation of HSC-Independent Hematopoietic Progenitors
2.7. Single Guide RNAs (sgRNA) Design and Nucleofection
2.8. CFU-C Assays
2.9. Cell Cultures
2.10. Statistical Analysis
3. Results
3.1. In Vivo Introduction of Mll-Af9 Inter-Chromosomal Translocation in Embryonic HSPCs Results in a Transplantable Myeloproliferative Disease
3.2. Transplantation of HSC-Independent Hematopoietic Progenitors Carrying Mll-Af9 Translocation Induces a Myeloid Neoplastic Disease
3.3. CRISPR/Cas9 Engineering of the Mll-Af9 Translocation in HSC-Independent Hematopoietic Progenitors Triggers an Aberrant Self-Renewal Program
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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Barone, C.; Orsenigo, R.; Cazzola, A.; D’Errico, E.; Patelli, A.; Quattrini, G.; Vergani, B.; Bombelli, S.; De Marco, S.; D’Orlando, C.; et al. Hematopoietic Stem Cell (HSC)-Independent Progenitors Are Susceptible to Mll-Af9-Induced Leukemic Transformation. Cancers 2023, 15, 3624. https://doi.org/10.3390/cancers15143624
Barone C, Orsenigo R, Cazzola A, D’Errico E, Patelli A, Quattrini G, Vergani B, Bombelli S, De Marco S, D’Orlando C, et al. Hematopoietic Stem Cell (HSC)-Independent Progenitors Are Susceptible to Mll-Af9-Induced Leukemic Transformation. Cancers. 2023; 15(14):3624. https://doi.org/10.3390/cancers15143624
Chicago/Turabian StyleBarone, Cristiana, Roberto Orsenigo, Anna Cazzola, Elisabetta D’Errico, Arianna Patelli, Giulia Quattrini, Barbara Vergani, Silvia Bombelli, Sofia De Marco, Cristina D’Orlando, and et al. 2023. "Hematopoietic Stem Cell (HSC)-Independent Progenitors Are Susceptible to Mll-Af9-Induced Leukemic Transformation" Cancers 15, no. 14: 3624. https://doi.org/10.3390/cancers15143624