New advances in the pathogenesis and therapy of essential thrombocythemia Journal Article
| Authors: | Levine, R. L.; Heaney, M. |
| Article Title: | New advances in the pathogenesis and therapy of essential thrombocythemia |
| Abstract: | Essential thrombocythemia (ET) is a hematopoietic disorder that manifests clinically as thrombocytosis, and patients with ET are at increased risk for developing thrombosis, myelofibrosis, and transformation to acute myeloid leukemia. Although ET was recognized as a distinct clinical syndrome more than 6 decades ago and was classified as a myeloproliferative neoplasm (MPN) by William Dameshek in 1951, the molecular pathogenesis of ET remained unknown until 2005, when activating mutations in the JAK2 tyrosine kinase (JAK2V617F) were identified in a significant proportion of patients with ET, polycythemia vera (PV) and primary myelofibrosis (PMF). In addition, subsequent studies have identified gain-of-function mutations in the thrombopoietin receptor (MPL) in a subset of patients with JAK2V617F-negative ET, suggesting that JAK2 activation by distinct mechanisms contributes to the pathogenesis of ET. Despite these important observations, important questions remain regarding the role of JAK2/MPL mutations in ET pathogenesis, the etiology of JAK2/MPL negative ET, the factors that distinguish ET from other MPNs with the JAK2V617F mutation, and the role of JAK2-targeted therapies for the treatment of these MPNs. |
| Keywords: | acute granulocytic leukemia; genetics; mutation; leukemia, myeloid, acute; janus kinase 2; thrombopoietin receptor; review; thrombocyte; erythropoiesis; amino acid substitution; chromosomes, human, pair 9; enzymology; uniparental disomy; homozygote; codon; granulocyte; thrombocytosis; thrombocythemia; blood platelets; thrombocythemia, essential; jak2 protein, human; chromosome 9; receptors, thrombopoietin; thrombopoiesis; thrombocytopoiesis; glucose 6 phosphate dehydrogenase; glucosephosphate dehydrogenase; granulocytes |
| Journal Title: | Hematology-American Society of Hematology Education Program |
| ISSN: | 1520-4391 |
| Publisher: | American Society of Hematology |
| Date Published: | 2008-01-01 |
| Start Page: | 76 |
| End Page: | 82 |
| Language: | English |
| PUBMED: | 19074062 |
| PROVIDER: | scopus |
| DOI: | 10.1182/asheducation-2008.1.76 |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 2" - "Export Date: 17 November 2011" - "Source: Scopus" |
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