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 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
Author
Faculty/Department
Faculty of Medicine and Health Sciences
University Hospital Antwerp
Publication type
article
Publication
Basel ,
Subject
Human medicine
Source (journal)
Acta haematologica. - Basel
Volume/pages
133(2015) :1 , p. 36-51
ISSN
0001-5792
ISI
000342739500008
Carrier
E
Target language
English (eng)
Full text (Publishers DOI)
Affiliation
University of Antwerp
Abstract
The Polycythemia Vera Study Group (PVSG) and WHO classifications distinguished the Philadelphia (Ph-1) chromosome- positive chronic myeloid leukemia from the Ph-1-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(V617F) mutation, indicating prodromal PV. The positive predictive value of a JAK2(V617F) PCR test is 95% for the diagnosis of PV, and about 50% for ET and MF. The WHO-defined JAK2(V617F)-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(V617F)-positive ET and PV; JAK2 wild-type ET carrying the MPL515; 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(V617F) mutation load is low in heterozygous normocellular WHO-ET. The JAK2(V617F) 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 MPL515 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(V617F) mutated ET, EMGM and PV, and neither in JAK2 wild-type ET carrying the MPL515 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. (C) 2014 S. Karger AG, Basel
E-info
http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000342739500008&DestLinkType=RelatedRecords&DestApp=ALL_WOS&UsrCustomerID=ef845e08c439e550330acc77c7d2d848
http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000342739500008&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=ef845e08c439e550330acc77c7d2d848
http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000342739500008&DestLinkType=CitingArticles&DestApp=ALL_WOS&UsrCustomerID=ef845e08c439e550330acc77c7d2d848
Handle