Naslov
Role of neoplastic monocyte-derived fibrocytes in primary myelofibrosis

Autori
Verstovsek, Srdan ; Manshouri, Taghi ; Pilling, Darrell ; Bueso-Ramos, Carlos E. ; Newberry, Kate J. ; Prijić, Sanja ; Knez, Liza ; Božinović, Ksenija ; Harris, David M. ; Spaeth, Erica L. ; Post, Sean M ; Multani, Asha S. ; Rampal, Raajit K. ; Ahn, Jihae ; Levine, Ross L. ; Creighton, Chad J. ; Kantarjian, Hagop M. ; Estrov, Zeev

Izvornik
The Journal of experimental medicine (0022-1007) 213 (2016), 9; 1723-1740

Vrsta, podvrsta i kategorija rada
Radovi u časopisima, članak, znanstveni

Ključne riječi
Primary myelofibrosis ; bone marrow (BM) fibrosis ; monocyte-derived fibrocytes ; serum amyloid P

Sažetak
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.

Izvorni jezik
Engleski

Znanstvena područja
Temeljne medicinske znanosti

POVEZANOST RADA