title: Bone marrow fibrosis in primary myelofibrosis: pathogenic mechanisms and the role of TGF-β.
abstract: Primary myelofibrosis (PMF) is a Philadelphia chromosome negative myeloproliferative neoplasm (MPN) with adverse prognosis and is associated with bone marrow fibrosis and extramedullary hematopoiesis. Even though the discovery of the Janus kinase 2 (JAK2), thrombopoietin receptor (MPL) and calreticulin (CALR) mutations have brought new insights into the complex pathogenesis of MPNs, the etiology of fibrosis is not well understood. Furthermore, since JAK2 inhibitors do not lead to reversal of fibrosis further understanding of the biology of fibrotic process is needed for future therapeutic discovery. Transforming growth factor beta (TGF-β) is implicated as an important cytokine in pathogenesis of bone marrow fibrosis. Various mouse models have been developed and have established the role of TGF-β in the pathogenesis of fibrosis. Understanding the molecular alterations that lead to TGF-β mediated effects on bone marrow microenvironment can uncover newer therapeutic targets against myelofibrosis. Inhibition of the TGF-β pathway in conjunction with other therapies might prove useful in the reversal of bone marrow fibrosis in PMF.
authors.affiliation: 1 Steward Carney Hospital, 2100 Dorchester Avenue, Dorchester, MA, USA ; 2 Albert Einstein College of Medicine, Bronx, NY, USA ; 3 University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA.
authors.forename: Archana
authors.initials: A
authors.lastname: Agarwal
authors.affiliation: 1 Steward Carney Hospital, 2100 Dorchester Avenue, Dorchester, MA, USA ; 2 Albert Einstein College of Medicine, Bronx, NY, USA ; 3 University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA.
authors.forename: Kerry
authors.initials: K
authors.lastname: Morrone
authors.affiliation: 1 Steward Carney Hospital, 2100 Dorchester Avenue, Dorchester, MA, USA ; 2 Albert Einstein College of Medicine, Bronx, NY, USA ; 3 University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA.
authors.forename: Matthias
authors.initials: M
authors.lastname: Bartenstein
authors.affiliation: 1 Steward Carney Hospital, 2100 Dorchester Avenue, Dorchester, MA, USA ; 2 Albert Einstein College of Medicine, Bronx, NY, USA ; 3 University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA.
authors.forename: Zhizhuang Joe
authors.initials: ZJ
authors.lastname: Zhao
authors.affiliation: 1 Steward Carney Hospital, 2100 Dorchester Avenue, Dorchester, MA, USA ; 2 Albert Einstein College of Medicine, Bronx, NY, USA ; 3 University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA.
authors.forename: Amit
authors.initials: A
authors.lastname: Verma
authors.affiliation: 1 Steward Carney Hospital, 2100 Dorchester Avenue, Dorchester, MA, USA ; 2 Albert Einstein College of Medicine, Bronx, NY, USA ; 3 University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA.
authors.forename: Swati
authors.initials: S
authors.lastname: Goel
keywords: GATA-1; Primary myelofibrosis (PMF); thrombopoietin (TPO); transforming growth factor beta 1 (TGF-β1)