Role of neoplastic monocyte-derived fibrocytes in primary myelofibrosis

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

doi:10.1084/jem.20160283

Role of neoplastic monocyte-derived fibrocytes in primary myelofibrosis

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

Research output: Contribution to journal › Article › peer-review

117 Scopus citations

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.

Original language	English (US)
Pages (from-to)	1723-1740
Number of pages	18
Journal	Journal of Experimental Medicine
Volume	213
Issue number	9
DOIs	https://doi.org/10.1084/jem.20160283
State	Published - Aug 22 2016

ASJC Scopus subject areas

Immunology and Allergy
Immunology

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Verstovsek, S., Manshouri, T., Pilling, D., Bueso-Ramos, C. E., Newberry, K. J., Prijic, S., Knez, L., Bozinovic, K., Harris, D. M., Spaeth, E. L., Post, S. M., Multani, A. S., Rampal, R. K., Ahn, J., Levine, R. L., Creighton, C. J., Kantarjian, H. M., & Estrov, Z. (2016). Role of neoplastic monocyte-derived fibrocytes in primary myelofibrosis. Journal of Experimental Medicine, 213(9), 1723-1740. https://doi.org/10.1084/jem.20160283

Verstovsek, S, Manshouri, T, Pilling, D, Bueso-Ramos, CE, Newberry, KJ, Prijic, S, Knez, L, Bozinovic, K, Harris, DM, Spaeth, EL, Post, SM , Multani, AS, Rampal, RK, Ahn, J, Levine, RL, Creighton, CJ, Kantarjian, HM & Estrov, Z 2016, 'Role of neoplastic monocyte-derived fibrocytes in primary myelofibrosis', Journal of Experimental Medicine, vol. 213, no. 9, pp. 1723-1740. https://doi.org/10.1084/jem.20160283

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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.",

author = "Srdan Verstovsek and Taghi Manshouri and Darrell Pilling and Bueso-Ramos, {Carlos E.} and Newberry, {Kate J.} and Sanja Prijic and Liza Knez and Ksenija Bozinovic and Harris, {David M.} and Spaeth, {Erika L.} and Post, {Sean M.} and Multani, {Asha S.} and Rampal, {Raajit K.} and Jihae Ahn and Levine, {Ross L.} and Creighton, {Chad J.} and Kantarjian, {Hagop M.} and Zeev Estrov",

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AU - Bueso-Ramos, Carlos E.

AU - Newberry, Kate J.

AU - Prijic, Sanja

AU - Knez, Liza

AU - Bozinovic, Ksenija

AU - Harris, David M.

AU - Spaeth, Erika L.

AU - Post, Sean M.

AU - Multani, Asha S.

AU - Rampal, Raajit K.

AU - Ahn, Jihae

AU - Levine, Ross L.

AU - Creighton, Chad J.

AU - Kantarjian, Hagop M.

AU - Estrov, Zeev

PY - 2016/8/22

Y1 - 2016/8/22

N2 - 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.

AB - 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.

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Role of neoplastic monocyte-derived fibrocytes in primary myelofibrosis

Abstract

ASJC Scopus subject areas

MD Anderson CCSG core facilities

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