title: Primary myelofibrosis and its targeted therapy.
abstract: Primary myelofibrosis is a unique entity among BCR-ABL-negative myeloproliferative diseases, manifesting as bone marrow fibrosis and pancytopenia. Considerable evidence indicates that genetic and epigenetic abnormalities can result in defective clonal hematopoietic stem cell proliferation in addition to bone marrow microenvironment alteration. The "bad seeds in bad soil" theory illustrates the orchestrating efforts of hematopoietic stem cells, stromal cells, and their surrounding signaling molecules in myelofibrosis progression and malignancy transformation, though the exact mechanism of myelofibrosis is still not clear. This study reviews current concepts and questions regarding the pathogenesis of primary myelofibrosis and discusses the emerging targeted therapy aimed at restoring normal bone marrow environment and halting bone marrow fibrotic deterioration.
authors.affiliation: Department of Medicine, Duke University School of Medicine, Durham, NC, USA.
authors.forename: Lindsey
authors.initials: L
authors.lastname: Shantzer
authors.affiliation: Department of Medicine, Penn State University College of Medicine, Hershey, PA, USA.
authors.forename: Kristin
authors.initials: K
authors.lastname: Berger
authors.affiliation: Department of Medicine, Penn State University College of Medicine, Hershey, PA, USA. jpu2@jhmi.edu.|Department of Pathology, Pennsylvania State University College of Medicine, Hershey, PA, USA. jpu2@jhmi.edu.|Penn State Hershey Cancer Institute, Pennsylvania State University College of Medicine, Hershey, PA, USA. jpu2@jhmi.edu.
authors.forename: Jeffrey J
authors.initials: JJ
authors.lastname: Pu
mesh_terms: D000818:Animals; D002986:Clinical Trials as Topic / Q000379:methods; D016503:Drug Delivery Systems / Q000379:methods / Q000639:trends*; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods / Q000639:trends*; D006801:Humans; D053612:Janus Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D009570:Nitriles; D055728:Primary Myelofibrosis / Q000175:diagnosis / Q000201:enzymology / Q000628:therapy*; D011720:Pyrazoles / Q000008:administration & dosage; D011743:Pyrimidines
chemical_list: D009570:Nitriles; D011720:Pyrazoles; D011743:Pyrimidines; C540383:ruxolitinib; D053612:Janus Kinases
keywords: Bone marrow microenvironments; Genetic and epigenetic abnormality; Hematopoietic bone marrow stem cell; Primary myelofibrosis; Target therapy