Skoda RC 2009 Major progress in understanding the pathogenesis in patients with thrombocytosis has been made by identifying mutations in the key regulators of thrombopoietin: the thrombopoietin receptor MPL and JAK2. Together, these mutations can be found in 50% to 60% of patients with essential thrombocythemia or primary myelofibrosis and in 10% to 20% of hereditary thrombocytosis. A decrease in expression of the Mpl protein can cause thrombocytosis even in the absence of mutations in the coding sequence, due to a shift in the balance between stimulation of signaling in megakaryopoiesis and removal of thrombopoietin by receptor mediated internalization in platelets. When present in a heterozygous state the JAK2-V617F mutation preferentially stimulates megakaryopoiesis and in most cases manifests as essential thrombocythemia (ET), whereas homozygous JAK2-V617F reduces megakaryopoiesis in favor of increased erythropoiesis, resulting in polycythemia vera and/or myelofibrosis. In 30% to 40% of patients with ET or primary myelofibrosis (PMF) and in 80% to 90% of pedigrees with hereditary thrombocytosis the disease-causing gene remains unknown. Ongoing genetic and genomic screens have identified genes that, when mutated, can cause thrombocytosis in mouse models. A more complete picture of the pathways that regulate megakaryopoisis and platelet production will be important for finding new ways of controlling platelet production in patients with thrombocytosis. https://sonar.ch/global/documents/228062 eng info:eu-repo/semantics/altIdentifier/doi/10.1182/asheducation-2009.1.159 info:eu-repo/semantics/altIdentifier/pmid/20008195 Hematology. American Society of Hematology. Education Program. - 2009 Adult Amino Acid Substitution Animals Disease Models, Animal Humans Janus Kinase 2 Mice Mice, Inbred C57BL Mutation Mutation, Missense Polycythemia Vera Primary Myelofibrosis Receptors, Thrombopoietin Recombinant Fusion Proteins STAT Transcription Factors Thrombocythemia, Essential Thrombocytosis Thrombopoiesis Thrombopoietin Transduction, Genetic Thrombocytosis. http://purl.org/coar/resource_type/c_6501