Inhibiting the alarmin-driven hematopoiesis-stromal cell crosstalk in primary myelofibrosis ameliorates bone marrow fibrosis.

ABSTRACT: Inflammation from the hematopoietic compartment is a critical driver of fibrosis and cytopenias in myeloproliferative neoplasms (MPNs). We previously demonstrated that tasquinimod ameliorates the MPN phenotype, reducing splenomegaly and normalizing fibrosis in a JAK2V617F-driven preclinical model. Using bulk RNA sequencing, we now show that tasquinimod primarily targets the malignant JAK2V617F hematopoietic clone, particularly affecting megakaryocytes and monocytes. Tasquinimod downregulates pro-proliferative pathways, MYC targets, and mTORC signaling, while increasing apoptosis in particularly in JAK2V617F mutant cells. Our data reveal that tasquinimod reverses TGFβ-driven fibrotic reprogramming of megakaryocytes and monocytes. This reversal is crucial for mitigating the pro-fibrotic inte

SUBMITTER: Gleitz HFE 

PROVIDER: S-EPMC12351185 | biostudies-literature | 2025 Aug

REPOSITORIES: biostudies-literature