The role of the extracellular matrix in primary myelofibrosis

Abstract

Primary myelofibrosis (PMF) is a myeloproliferative neoplasm that arises from clonal proliferation of hematopoietic stem cells and leads to progressive bone marrow (BM) fibrosis. While cellular mutations involved in the development of PMF have been heavily investigated, noteworthy is the important role the extracellular matrix (ECM) plays in the progression of BM fibrosis. This review surveys ECM proteins contributors of PMF, and highlights how better understanding of the control of the ECM within the BM niche may lead to combined therapeutic options in PMF.

Figure 1

Schematic presentation of major components in ECM derived from MKs and involved in PMF progression. The parentheses include reference numbers corresponding to the illustrated pathway. BM, bone marrow; bFGF, basic fibroblast growth factor; ECM, extracellular matrix; IL-1β, interleukin-1 beta; LOX, lysyl oxidase; MK, megakaryocyte; MMP, matrix metalloproteinase; MSC, mesenchymal stromal cell; PDGF-R, PDGF receptor; TGF-β, transforming factor beta; TIMP, tissue inhibitor of metalloproteinases; TSP-1, thrombospondin-1; PDGF, platelet derived growth factor; VEGF, vascular endothelial growth factor.