title: Role of neoplastic monocyte-derived fibrocytes in primary myelofibrosis.
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.
authors.affiliation: Department of Leukemia, University of Texas MD Anderson Cancer Center, Houston, TX 77030.
authors.forename: Srdan
authors.identifier: 0000-0002-6912-8569
authors.initials: S
authors.lastname: Verstovsek
authors.affiliation: Department of Leukemia, University of Texas MD Anderson Cancer Center, Houston, TX 77030.
authors.forename: Taghi
authors.identifier: 0000-0003-1192-1465
authors.initials: T
authors.lastname: Manshouri
authors.affiliation: Department of Biology, Texas A&M University, College Station, TX 77433.
authors.forename: Darrell
authors.identifier: 0000-0002-7413-2773
authors.initials: D
authors.lastname: Pilling
authors.affiliation: Department of Hematopathology, University of Texas MD Anderson Cancer Center, Houston, TX 77030.
authors.forename: Carlos E
authors.initials: CE
authors.lastname: Bueso-Ramos
authors.affiliation: Department of Leukemia, University of Texas MD Anderson Cancer Center, Houston, TX 77030.
authors.forename: Kate J
authors.initials: KJ
authors.lastname: Newberry
authors.affiliation: Department of Leukemia, University of Texas MD Anderson Cancer Center, Houston, TX 77030.
authors.forename: Sanja
authors.identifier: 0000-0002-3934-3874
authors.initials: S
authors.lastname: Prijic
authors.affiliation: Department of Leukemia, University of Texas MD Anderson Cancer Center, Houston, TX 77030.
authors.forename: Liza
authors.initials: L
authors.lastname: Knez
authors.affiliation: Department of Leukemia, University of Texas MD Anderson Cancer Center, Houston, TX 77030.
authors.forename: Ksenija
authors.identifier: 0000-0001-6840-6689
authors.initials: K
authors.lastname: Bozinovic
authors.affiliation: Department of Leukemia, University of Texas MD Anderson Cancer Center, Houston, TX 77030.
authors.forename: David M
authors.identifier: 0000-0003-2419-3735
authors.initials: DM
authors.lastname: Harris
authors.affiliation: Department of Leukemia, University of Texas MD Anderson Cancer Center, Houston, TX 77030.
authors.forename: Erika L
authors.identifier: 0000-0002-5397-3493
authors.initials: EL
authors.lastname: Spaeth
authors.affiliation: Department of Leukemia, University of Texas MD Anderson Cancer Center, Houston, TX 77030.
authors.forename: Sean M
authors.initials: SM
authors.lastname: Post
authors.affiliation: Department of Genetics, University of Texas MD Anderson Cancer Center, Houston, TX 77030.
authors.forename: Asha S
authors.identifier: 0000-0002-6989-8627
authors.initials: AS
authors.lastname: Multani
authors.affiliation: Leukemia Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY 10065.
authors.forename: Raajit K
authors.identifier: 0000-0002-0355-6368
authors.initials: RK
authors.lastname: Rampal
authors.affiliation: Human Oncology and Pathogenesis Program, Gerstner Sloan Kettering School of Biomedical Sciences, New York, NY 10065.
authors.forename: Jihae
authors.initials: J
authors.lastname: Ahn
authors.affiliation: Leukemia Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY 10065.
authors.forename: Ross L
authors.initials: RL
authors.lastname: Levine
authors.affiliation: Division of Biostatistics, Dan L. Duncan Cancer Center, Baylor College of Medicine, Houston, TX 77030.
authors.forename: Chad J
authors.identifier: 0000-0002-6090-703X
authors.initials: CJ
authors.lastname: Creighton
authors.affiliation: Department of Leukemia, University of Texas MD Anderson Cancer Center, Houston, TX 77030.
authors.forename: Hagop M
authors.initials: HM
authors.lastname: Kantarjian
authors.affiliation: Department of Leukemia, University of Texas MD Anderson Cancer Center, Houston, TX 77030 zestrov@mdanderson.org.
authors.forename: Zeev
authors.initials: Z
authors.lastname: Estrov
mesh_terms: D000818:Animals; D001853:Bone Marrow / Q000473:pathology; D016026:Bone Marrow Transplantation; D002478:Cells, Cultured; D005347:Fibroblasts / Q000187:drug effects / Q000502:physiology*; D005355:Fibrosis; D018398:Homeodomain Proteins / Q000494:pharmacology; D006801:Humans; D051379:Mice; D016513:Mice, SCID; D009000:Monocytes / Q000166:cytology*; D009570:Nitriles; D055728:Primary Myelofibrosis / Q000209:etiology* / Q000473:pathology; D011720:Pyrazoles / Q000494:pharmacology; D011743:Pyrimidines; D011994:Recombinant Proteins / Q000494:pharmacology; D000683:Serum Amyloid P-Component / Q000494:pharmacology
chemical_list: D018398:Homeodomain Proteins; D009570:Nitriles; C552898:PRM-151; D011720:Pyrazoles; D011743:Pyrimidines; D011994:Recombinant Proteins; D000683:Serum Amyloid P-Component; C540383:ruxolitinib