title: Fibroblast dynamics as an in vitro screening platform for anti-fibrotic drugs in primary myelofibrosis.
abstract: Although the cause for bone marrow fibrosis in patients with myelofibrosis remains controversial, it has been hypothesized that it is caused by extensive fibroblast proliferation under the influence of cytokines generated by the malignant megakaryocytes. Moreover, there is no known drug therapy which could reverse the process. We studied the fibroblasts in a novel system using the hanging drop method, evaluated whether the fibroblasts obtain from patients are part of the malignant clone of not and, using this system, we screen a large library of FDA-approved drugs to identify potential drugs candidates that might be useful in the treatment of this disease, specifically which would inhibit fibroblast proliferation and the development of bone marrow fibrosis. We have found that the BM fibroblasts are not part of the malignant clone, as previously suspected and two immunosuppressive medications-cyclosporine and mycophenolate mophetil, as most potent suppressors of the fibroblast collagen production thus potentially inhibitors of bone marrow fibrosis production in myelofibrosis.
authors.affiliation: Department of Hematology, Ion Chiricuta Oncology Institute, Cluj Napoca, Romania.|Research Center for Functional Genomics and Translational Medicine/Hematology, Iuliu Hatieganu University of Medicine and Pharmacy, Cluj Napoca, Romania.
authors.forename: Ciprian
authors.identifier: http://orcid.org/0000-0001-5500-1519
authors.initials: C
authors.lastname: Tomuleasa
authors.affiliation: Research Center for Functional Genomics and Translational Medicine, Iuliu Hatieganu University of Medicine and Pharmacy, Cluj Napoca, Romania.
authors.forename: Sonia
authors.initials: S
authors.lastname: Selicean
authors.affiliation: Research Center for Functional Genomics and Translational Medicine, Iuliu Hatieganu University of Medicine and Pharmacy, Cluj Napoca, Romania.
authors.forename: Grigore
authors.initials: G
authors.lastname: Gafencu
authors.affiliation: Research Center for Functional Genomics and Translational Medicine, Iuliu Hatieganu University of Medicine and Pharmacy, Cluj Napoca, Romania.
authors.forename: Bobe
authors.initials: B
authors.lastname: Petrushev
authors.affiliation: Research Center for Functional Genomics and Translational Medicine, Iuliu Hatieganu University of Medicine and Pharmacy, Cluj Napoca, Romania.
authors.forename: Laura
authors.initials: L
authors.lastname: Pop
authors.affiliation: Research Center for Functional Genomics and Translational Medicine, Iuliu Hatieganu University of Medicine and Pharmacy, Cluj Napoca, Romania.
authors.forename: Cristian
authors.initials: C
authors.lastname: Berce
authors.affiliation: Research Center for Functional Genomics and Translational Medicine, Iuliu Hatieganu University of Medicine and Pharmacy, Cluj Napoca, Romania.
authors.forename: Anca
authors.initials: A
authors.lastname: Jurj
authors.affiliation: Department of Genetics, Iuliu Hatieganu University of Medicine and Pharmacy, Cluj Napoca, Romania.
authors.forename: Adrian
authors.initials: A
authors.lastname: Trifa
authors.affiliation: Research Center for Functional Genomics and Translational Medicine, Iuliu Hatieganu University of Medicine and Pharmacy, Cluj Napoca, Romania.
authors.forename: Ana-Maria
authors.initials: AM
authors.lastname: Rosu
authors.affiliation: Research Center for Functional Genomics and Translational Medicine, Iuliu Hatieganu University of Medicine and Pharmacy, Cluj Napoca, Romania.
authors.forename: Sergiu
authors.initials: S
authors.lastname: Pasca
authors.affiliation: Research Center for Functional Genomics and Translational Medicine, Iuliu Hatieganu University of Medicine and Pharmacy, Cluj Napoca, Romania.
authors.forename: Lorand
authors.initials: L
authors.lastname: Magdo
authors.affiliation: Department of Hematology, Ion Chiricuta Oncology Institute, Cluj Napoca, Romania.
authors.forename: Mihnea
authors.initials: M
authors.lastname: Zdrenghea
authors.affiliation: Department of Hematology, Ion Chiricuta Oncology Institute, Cluj Napoca, Romania.
authors.forename: Delia
authors.initials: D
authors.lastname: Dima
authors.affiliation: Department of Stem Cell Transplantation, Fundeni Clinical Institute, Bucharest, Romania.
authors.forename: Alina
authors.initials: A
authors.lastname: Tanase
authors.affiliation: Department of Hematology, Ion Chiricuta Oncology Institute, Cluj Napoca, Romania.
authors.forename: Ioana
authors.initials: I
authors.lastname: Frinc
authors.affiliation: Department of Hematology, Ion Chiricuta Oncology Institute, Cluj Napoca, Romania.
authors.forename: Anca
authors.initials: A
authors.lastname: Bojan
authors.affiliation: Research Center for Functional Genomics and Translational Medicine, Iuliu Hatieganu University of Medicine and Pharmacy, Cluj Napoca, Romania.
authors.forename: Ioana
authors.initials: I
authors.lastname: Berindan-Neagoe
authors.affiliation: Division of Hematological Malignancies, Department of Oncology, Sidney Kimmel Comprehensive Cancer Center-The Johns Hopkins University School of Medicine, Baltimore, Maryland.
authors.forename: Gabriel
authors.initials: G
authors.lastname: Ghiaur
authors.affiliation: Division of Cancer Medicine, Department of Stem Cell Transplantation, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Stefan O
authors.initials: SO
authors.lastname: Ciurea
mesh_terms: D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects*; D003094:Collagen / Q000378:metabolism*; D016572:Cyclosporine / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D055808:Drug Discovery / Q000295:instrumentation*; D005347:Fibroblasts / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D005355:Fibrosis; D005786:Gene Expression Regulation; D057166:High-Throughput Screening Assays; D053614:Janus Kinase 2 / Q000235:genetics / Q000378:metabolism; D007700:Kinetics; D009154:Mutation; D009173:Mycophenolic Acid / Q000494:pharmacology*; D055728:Primary Myelofibrosis / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D016212:Transforming Growth Factor beta / Q000494:pharmacology
chemical_list: D016212:Transforming Growth Factor beta; D016572:Cyclosporine; D003094:Collagen; C507924:JAK2 protein, human; D053614:Janus Kinase 2; D009173:Mycophenolic Acid
keywords: anti-fibrotic drug screening; fibroblasts; primary myelofibrosis