Sofia Bentivegna, Marwa Almosailleakh, Lin-Pierre Zhao, Mikkel Bruhn Schuster, Sébastien Benquet, Alexander Balhuizen, Helga Fibiger Munch-Petersen, Lene Dissing Sjö, Mads Hald Andersen, Nicolas Dulphy, Bo Porse, Kirsten Grønbæk
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引用次数: 0
Abstract
Clonal hematopoiesis of indeterminate potential (CHIP) is a condition where blood or bone marrow cells carry mutations associated with hematological malignancies. Individuals with CHIP have an increased risk of developing hematological malignancies, atherosclerotic cardiovascular disease, and all-cause mortality. Bone marrow transplantation (BMT) of cells carrying CHIP mutations into irradiated mice are useful procedures to investigate the dynamics of clonal expansion and potential therapeutic strategies, but myeloablative conditioning can induce confounding effects. We established a non-conditioned BMT model using C57BL/6J-KitW-41J/J (W41) recipient mice to overcome the unwanted effects of irradiation. Conditional Tet2 deletion using tamoxifen was used to obtain Tet2-/- cells from donor mice. Total BM Tet2-/- cells were transplanted into W41 recipients, and longitudinal and terminal analyses at 10 months post-BMT were performed. We showed that W41 mice can be used for BMT procedures without myeloablative pre-conditioning. The transplantation of Tet2-/- BM cells led to a progressive expansion of the donor cells in W41 recipients. By modulating the numbers of Tet2-/- cells transplanted, recipient mice developed features of clonal hematopoiesis or myeloid malignancies. In conclusion, our model is an alternative to conventional irradiation-based transplantation models to study mechanisms underlying malignant hematopoiesis without confounding effects derived from pre-conditioning regimen.
期刊介绍:
Experimental Hematology & Oncology is an open access journal that encompasses all aspects of hematology and oncology with an emphasis on preclinical, basic, patient-oriented and translational research. The journal acts as an international platform for sharing laboratory findings in these areas and makes a deliberate effort to publish clinical trials with 'negative' results and basic science studies with provocative findings.
Experimental Hematology & Oncology publishes original work, hypothesis, commentaries and timely reviews. With open access and rapid turnaround time from submission to publication, the journal strives to be a hub for disseminating new knowledge and discussing controversial topics for both basic scientists and busy clinicians in the closely related fields of hematology and oncology.