title: Pathogenesis of myelofibrosis with myeloid metaplasia: lessons from mouse models of the disease.
abstract: The primary genetic lesion(s), as well as the biological processes responsible for the typical structural changes of the bone marrow microenvironment in idiopathic myelofibrosis, are still poorly understood, although a central role in disease pathogenesis has been attributed to the clonal proliferation and defective maturation of megakaryocytes. Two animal models of the disease have been described, that in the last few years significantly contributed to the elucidation of some of the pathogenetic steps of the human disease; these are represented by mice genetically modified to overexpress thrombopoietin and by knock-down mice with defective GATA-1 expression in megakaryocytes (GATA-1(low) mice). This review will outline these murine models, both characterized by extensive accumulation of megakaryocytes in hematopoietic tissues, and illustrate how they provided insights into the identification of some of the molecules and mechanisms responsible for the development of fibrosis and osteosclerosis that present major similarities with those observed in patients with idiopathic myelofibrosis.
authors.affiliation: Hematology Unit, University of Florence, AOC, Italy. a.vannucchi@dac.unifi.it
authors.forename: Alessandro M
authors.initials: AM
authors.lastname: Vannucchi
authors.forename: Anna Rita
authors.initials: AR
authors.lastname: Migliaccio
authors.forename: Francesco
authors.initials: F
authors.lastname: Paoletti
authors.forename: Hedia
authors.initials: H
authors.lastname: Chagraoui
authors.forename: Françoise
authors.initials: F
authors.lastname: Wendling
mesh_terms: D000818:Animals; D004268:DNA-Binding Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D004195:Disease Models, Animal; D050981:Erythroid-Specific DNA-Binding Factors; D050982:GATA1 Transcription Factor; D018014:Gene Transfer Techniques; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D055728:Primary Myelofibrosis / Q000276:immunology / Q000503:physiopathology*; D011506:Proteins / Q000378:metabolism; D013926:Thrombopoietin / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000276:immunology / Q000378:metabolism
chemical_list: D004268:DNA-Binding Proteins; D050981:Erythroid-Specific DNA-Binding Factors; D050982:GATA1 Transcription Factor; C494689:Gata1 protein, mouse; D011506:Proteins; D014157:Transcription Factors; D013926:Thrombopoietin