Dynamic assessment of myelofibrosis progression in myeloproliferative neoplasm mouse model using a minimally invasive evaluation system.

Abstract

Myelofibrosis (MF) is the most common complication of myeloproliferative neoplasms (MPNs)，which is markedly correlated with a dismal prognosis. Murine model such as the thrombopoietin receptor (MPL)W515L-mutant MPN mouse model functions as a crucial vehicle in disease research, is widely used in basic and applied research on MPNs and MF.However, the lack of methods for dynamic observation of MF progression hinders mechanistic studies and drug development for MF. Here we develop a sensitive, stable and minimally invasive MPN evaluation system to assess the evolution of myelofibrosis in murine model.Key peripheral blood parameters (WBC, RBC, HGB, HCT, PLT, and tumor cell proportion) from MPN mice were analyzed using PCA to reduce dimensionality and generate a comprehensive evaluation score (Y). Based on peripheral blood smear observations and predefined score cut-off values (0.59 and - 0.44), MPN was classified into mild, moderate, and severe stages. Validation conducted across diverse experimental settings yielded outcomes that were in alignment with the pathological grading of myelofibrosis. This system facilitated the dynamic monitoring of MF progression in applied research on pigment epithelium-derived factor treatment for MPN and basic studies on the role of NLRP inflammasomes in the bone marrow microenvironment. We believed that this minimally invasive evaluation system for grading MF severity in MPN mouse model will provide a potential tool for MPN pathogenesis research and targeted therapy development.