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Karger AG","issue":"1","license":[{"start":{"date-parts":[[2014,8,7]],"date-time":"2014-08-07T00:00:00Z","timestamp":1407369600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.karger.com\/Services\/SiteLicenses"},{"start":{"date-parts":[[2014,8,7]],"date-time":"2014-08-07T00:00:00Z","timestamp":1407369600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.karger.com\/Services\/SiteLicenses"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Acta Haematol"],"published-print":{"date-parts":[[2015]]},"abstract":"<jats:p>The Polycythemia Vera Study Group (PVSG) and WHO classifications distinguished the Philadelphia (Ph&lt;sup&gt;1&lt;\/sup&gt;) chromosome-positive chronic myeloid leukemia from the Ph&lt;sup&gt;1&lt;\/sup&gt;-negative myeloproliferative neoplasms (MPN) essential thrombocythemia (ET), polycythemia vera (PV) and primary myelofibrosis (MF) or primary megakaryocytic granulocytic myeloproliferation (PMGM). Half of PVSG\/WHO-defined ET patients show low serum erythropoietin levels and carry the JAK2&lt;sup&gt;V617F&lt;\/sup&gt; mutation, indicating prodromal PV. The positive predictive value of a JAK2&lt;sup&gt;V617F&lt;\/sup&gt; PCR test is 95% for the diagnosis of PV, and about 50% for ET and MF. The WHO-defined JAK2&lt;sup&gt;V617F&lt;\/sup&gt;-positive ET comprises three ET phenotypes at clinical and bone marrow level when the integrated WHO and European Clinical, Molecular and Pathological (ECMP) criteria are applied: normocellular ET (WHO-ET), hypercellular ET due to increased erythropoiesis (prodromal PV) and hypercellular ET associated with megakaryocytic granulocytic myeloproliferation (EMGM). Four main molecular types of clonal MPN can be distinguished: JAK2&lt;sup&gt;V617F&lt;\/sup&gt;-positive ET and PV; JAK2 wild-type ET carrying the MPL&lt;sup&gt;515&lt;\/sup&gt;; mutations in the calreticulin (CALR) gene in JAK2\/MPL wild-type ET and MF, and a small proportion of JAK2\/MPL\/CALR wild-type ET and MF patients. The JAK2&lt;sup&gt;V617F&lt;\/sup&gt; mutation load is low in heterozygous normocellular WHO-ET. The JAK2&lt;sup&gt;V617F&lt;\/sup&gt; mutation load in hetero-\/homozygous PV and EMGM is clearly related to MPN disease burden in terms of splenomegaly, constitutional symptoms and fibrosis. The JAK2 wild-type ET carrying the MPL&lt;sup&gt;515&lt;\/sup&gt; mutation is featured by clustered small and giant megakaryocytes with hyperlobulated stag-horn-like nuclei, in a normocellular bone marrow (WHO-ET), and lacks features of PV. JAK2\/MPL wild-type, CALR mutated hypercellular ET associated with PMGM is featured by dense clustered large immature dysmorphic megakaryocytes and bulky (cloud-like) hyperchromatic nuclei, which are never seen in WHO-ECMP-defined JAK2&lt;sup&gt;V617F&lt;\/sup&gt; mutated ET, EMGM and PV, and neither in JAK2 wild-type ET carrying the MPL&lt;sup&gt;515&lt;\/sup&gt; mutation. Two thirds of JAK2\/MPL wild-type ET and MF patients carry one of the CALR mutations as the cause of the third distinct MPN entity. WHO-ECMP criteria are recommended to diagnose, classify and stage the broad spectrum of MPN of various molecular etiologies.<\/jats:p>","DOI":"10.1159\/000358580","type":"journal-article","created":{"date-parts":[[2014,8,7]],"date-time":"2014-08-07T07:25:47Z","timestamp":1407396347000},"page":"36-51","source":"Crossref","is-referenced-by-count":31,"title":["Changing Concepts of Diagnostic Criteria of Myeloproliferative Disorders and the Molecular Etiology and Classification of Myeloproliferative Neoplasms: From Dameshek 1950 to Vainchenker 2005 and Beyond"],"prefix":"10.1159","volume":"133","author":[{"given":"Jan 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