Fig. 2: TLR-directed pathogenesis of cytopenic myelofibrosis (MF).
From: Biological drivers of clinical phenotype in myelofibrosis
JAK2V617F-mutant HSPC overexpress the heterodimeric alarmin, S100A8/S100A9, also termed calprotectin. Paracrine stimulation of TLR4 in bone marrow mesenchymal stromal cells (MSCs) instructs aberrant upregulation by MSCs. Calprotectin from MSCs stimulates the TLR4/Myddosome pathway in megakaryocytes to elaborate TGF-β and drive fibrosis progression, splenomegaly and exacerbation of cytopenias in MF.
