title: Molecular pathogenesis of Philadelphia chromosome negative myeloproliferative disorders.
abstract: We summarize the current knowledge on molecular alterations in myeloproliferative disorders (MPD), in particular altered in vitro responses of progenitor cells, cytokine signaling, gene expression patterns and genetic lesions. Newly characterized markers, such as altered expression of polycythemia rubra vera-1 (PRV-1) and the thrombopoietin receptor (c-MPL) as well as deletions on chromosome 20q (del20q) and loss of heterozygosity on chromosome 9p (9pLOH) provide an opportunity to diagnose and identify subpopulations of MPD patients. Furthermore, we review familial syndromes that share phenotypic features with sporadic MPD. In some of these families, mutations in the genes for thrombopoietin (TPO), c-MPL, EPO-receptor and the von Hippel-Lindau (VHL) gene have been shown to cause the disease. However, in the majority of familial cases the molecular causes remain unknown. Some of these families display clonal hematopoiesis and other features previously only found in sporadic MPD. Elucidating the molecular defect(s) in these pedigrees will likely be relevant for understanding sporadic MPD pathogenesis.
authors.affiliation: Department of Research, Experimental Hematology, Basel University Hospital, Hebelstrasse 20, 4031 Basel, Switzerland. r.kralovics@unibas.ch
authors.forename: Robert
authors.initials: R
authors.lastname: Kralovics
authors.forename: Radek C
authors.initials: RC
authors.lastname: Skoda
mesh_terms: D002352:Carrier Proteins / Q000235:genetics; D002869:Chromosome Aberrations; D003598:Cytoskeletal Proteins; D058851:GPI-Linked Proteins; D005819:Genetic Markers / Q000235:genetics; D006801:Humans; D007519:Isoantigens / Q000235:genetics; D008562:Membrane Glycoproteins / Q000235:genetics; D018832:Molecular Chaperones; D009154:Mutation; D009196:Myeloproliferative Disorders / Q000145:classification / Q000235:genetics* / Q000473:pathology; D010677:Philadelphia Chromosome; D011518:Proto-Oncogene Proteins / Q000235:genetics; D011956:Receptors, Cell Surface; D018121:Receptors, Cytokine / Q000235:genetics; D017467:Receptors, Erythropoietin / Q000235:genetics; D053628:Receptors, Thrombopoietin; D013926:Thrombopoietin / Q000235:genetics
chemical_list: C407242:CD177 protein, human; D002352:Carrier Proteins; D003598:Cytoskeletal Proteins; D058851:GPI-Linked Proteins; D005819:Genetic Markers; D007519:Isoantigens; D008562:Membrane Glycoproteins; D018832:Molecular Chaperones; D011518:Proto-Oncogene Proteins; D011956:Receptors, Cell Surface; D018121:Receptors, Cytokine; D017467:Receptors, Erythropoietin; D053628:Receptors, Thrombopoietin; C108825:VBP1 protein, human; C082218:MPL protein, human; D013926:Thrombopoietin