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Bone Marrow Transplantation Procedures in Mice to Study Clonal Hematopoiesis
Published on: May 26, 2021
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Clonal competition in BcrAbl-driven leukemia: how transplantations can accelerate clonal conversion.
Kerstin Cornils1,2, Lars Thielecke3, Doreen Winkelmann4
1Research Department Cell and Gene Therapy, Department of Stem Cell Transplantation, University Medical Center Hamburg-Eppendorf, Hamburg, Germany. kcornils@uke.de.
Molecular Cancer
|July 16, 2017
Summary
Cancer clonal competition dynamics are influenced by environmental context, not just mutations. Differential engraftment capacity explains dominant clone success in BcrAbl-induced leukemia.
Area of Science:
- Oncology
- Cancer Biology
- Hematopoiesis
Background:
- Clonal competition in cancer involves cell progeny outcompeting others based on acquired mutations.
- While mutation patterns are known, the dynamics of clonal selection remain underexplored.
Purpose of the Study:
- To investigate the dynamics of clonal competition in BcrAbl-induced leukemia.
- To understand the factors driving clonal selection in cancer development.
Main Methods:
- Utilized a γ-retroviral vector library with genetic barcodes for BcrAbl-induced leukemia studies.
- Analyzed clonal growth dynamics in vitro and in vivo using transplanted mice.
- Applied a mathematical model of hematopoietic tissue maintenance to analyze clonal success.
Main Results:
- Observed moderate changes in clonal abundance in vitro.
- Monoclonal leukemias developed in 6/30 mice post-transplantation, originating from only two distinct BcrAbl clones.
- Differential engraftment capacity of dominant clones, supported by increased BcrAbl transcript levels, explained observed outcomes.
Conclusions:
- Clonal competition is not solely mutation-driven but is highly dependent on environmental selection mechanisms.
- Engraftment capacity plays a crucial role in determining the success of competing clones in leukemia.
