[Experimental model systems of primary myelofibrosis].
Key claim: Cellular, animal, and organoid experimental models of primary myelofibrosis are essential for studying JAK2/CALR/MPL-driven pathogenesis and screening therapies, but each model class has important limitations that constrain drug development.
Abstract
Myeloproliferative neoplasms are a group of clonal proliferative diseases originating from hematopoietic stem cells, with a risk of transformation to acute myeloid leukemia. Primary myelofibrosis (PMF) is a subtype of myeloproliferative neoplasms. Mutations in Janus kinase 2 (JAK2), calreticulin (CALR), and thrombopoietin receptor (MPL) genes are the main pathogenic factors in PMF patients. Current therapeutic strategies, including JAK2 inhibitors, are only effective in a subset of PMF patients, highlighting an urgent need for the development of novel interventions. Experimental models of PMF, including cellular models, animal models, andorganoid models, play crucial roles in exploring pathogenesis and screening potential therapeutic agents. This review comprehensively summarizes these experimental model systems, compares the advantages and disadvantages of different models, and discusses the limitations of current research and prospects for future directions, in order to provide assistance for the development of therapeutic strategies for PMF.
Why this matters
Cellular, animal, and organoid experimental models of primary myelofibrosis are essential for studying JAK2/CALR/MPL-driven pathogenesis and screening therapies, but each model class has important limitations that constrain drug development.