Year: 2016
Type: article
Abstract: Primary myelofibrosis (PMF) is a fatal neoplastic disease characterized by clonal myeloproliferation and progressive bone marrow (BM) fibrosis thought to be induced by mesenchymal stromal cells stimulated by overproduced growth factors. However, tissue fibrosis in other diseases is associated with monocyte-derived fibrocytes. Therefore, we sought to determine whether fibrocytes play a role in the induction of BM fibrosis in PMF. In this study, we show that BM from patients with PMF harbors an abundance of clonal, neoplastic collagen- and fibronectin-producing fibrocytes. Immunodeficient mice transplanted with myelofibrosis patients' BM cells developed a lethal myelofibrosis-like phenotype. Treatment of the xenograft mice with the fibrocyte inhibitor serum amyloid P (SAP; pentraxin-2) significantly prolonged survival and slowed the development of BM fibrosis. Collectively, our data suggest that neoplastic fibrocytes contribute to the induction of BM fibrosis in PMF, and inhibiting fibrocyte differentiation with SAP may interfere with this process.
DOI: 10.1084/jem.20160283
Authors: Srdan Verstovsek, Taghi Manshouri, Darrell Pilling, Carlos E. Bueso-Ramos, Kate J. Newberry, Sanja Prijic, Liza Knez, Ksenija Bozinovic, David M. Harris, Erika L. Spaeth, Sean M. Post, Asha S. Multani, Raajit K. Rampal, Jihae Ahn, Ross L. Levine, Chad J. Creighton, Hagop M. Kantarjian, Zeev Estrov
Language: English
Subfield: Genetics
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
OpenAlex ID: W2493190817