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Updated: Oct 3, 2025
Transduction-Transplantation Mouse Model of Myeloproliferative Neoplasm
Published on: December 22, 2016
Lessons from mouse models of MPN
Camelia Benlabiod1, Tracy Dagher1, Caroline Marty1
1INSERM, UMR 1287, Gustave Roussy, Villejuif, France; Université Paris-Saclay, UMR 1287, Gustave Roussy, Villejuif, France; Gustave Roussy, UMR 1287, Villejuif, France.
Abstract:
Over the past decades, a variety of MPN mouse models have been developed to express in HSC the main mutations identified in patients: JAK2V617F, CALRdel52 or ins5 and MPLW515L. These models mimic quite faithfully human PV or ET with their natural evolutions into MF and their hemostasis complications, demonstrating the driver function of these mutations in MPN. Here, we review these models and show how they have improved our general understanding of MPN regarding (1) the mechanisms of fibrosis, thrombosis/hemorrhages and disease initiation, (2) the roles of additional mutations and signaling pathways in disease progression and (3) the preclinical development of novel therapies. We also address controversial results between these models and remind how these models may differ from human MPN onset and also how basically mice are not humans, encouraging caution when one draw lessons from mice to humans. Furthermore, the contribution of germline genetic predisposition, HSC and niche aging, metabolic, oxidative, replicative or genotoxic stress, inflammation, immune escape and additional mutations need to be considered in further investigations to encompass the full complexity of human MPN in mice.
Insights
Mouse models expressing key mutations (JAK2, CALR, MPL) have advanced myeloproliferative neoplasms (MPN) research, aiding understanding of disease mechanisms and therapy development.
Area of Science:
- Hematology
- Oncology
- Genetics
Background:
- Myeloproliferative neoplasms (MPNs) are driven by mutations like JAK2V617F, CALR, and MPLW515L.
- Mouse models are crucial for studying MPN pathogenesis and evaluating treatments.
Purpose of the Study:
- To review existing MPN mouse models.
- To highlight their contributions to understanding MPN mechanisms and preclinical therapy development.
- To discuss model limitations and the complexity of human MPN.
Main Methods:
- Review of established MPN mouse models.
- Analysis of how these models recapitulate human MPN phenotypes.
- Examination of their utility in investigating disease initiation, progression, and treatment.
Main Results:
- MPN mouse models accurately mimic human polycythemia vera (PV) and essential thrombocythemia (ET), including progression to myelofibrosis (MF).
- These models have elucidated mechanisms of fibrosis, thrombosis, and disease initiation.
- They have also aided in understanding the role of additional mutations and signaling pathways in disease progression and in preclinical therapy testing.
Conclusions:
- MPN mouse models are valuable tools for studying disease biology and developing therapies.
- Caution is advised when extrapolating findings from mice to humans due to species differences.
- Future research should incorporate factors like germline predisposition, aging, and microenvironment to fully capture human MPN complexity.
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