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J Exp Med. 2016 Aug 22;213(9):1723-40. doi: 10.1084/jem.20160283. Epub 2016 Aug 1.

Role of neoplastic monocyte-derived fibrocytes in primary myelofibrosis.

Author information

1
Department of Leukemia, University of Texas MD Anderson Cancer Center, Houston, TX 77030.
2
Department of Biology, Texas A&M University, College Station, TX 77433.
3
Department of Hematopathology, University of Texas MD Anderson Cancer Center, Houston, TX 77030.
4
Department of Genetics, University of Texas MD Anderson Cancer Center, Houston, TX 77030.
5
Leukemia Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY 10065.
6
Human Oncology and Pathogenesis Program, Gerstner Sloan Kettering School of Biomedical Sciences, New York, NY 10065.
7
Division of Biostatistics, Dan L. Duncan Cancer Center, Baylor College of Medicine, Houston, TX 77030.
8
Department of Leukemia, University of Texas MD Anderson Cancer Center, Houston, TX 77030 zestrov@mdanderson.org.

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.

PMID:
27481130
PMCID:
PMC4995084
DOI:
10.1084/jem.20160283
[Indexed for MEDLINE]
Free PMC Article

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