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Abstract

Research Article

The PVSG/WHO versus the Rotterdam European clinical, molecular and pathological diagnostic criteria for the classification of myeloproliferative disorders and myeloproliferative neoplasms (MPD/MPN): From Dameshek to Georgii, Vainchenker and Michiels 1950-2018

Jan Jacques Michiels* and Hendrik De Raeve

Published: 17 April, 2019 | Volume 2 - Issue 1 | Pages: 027-050

The present article extends the PVSG-WHO criteria into a simplified set of Rotterdam and European Clinical, Molecular and Pathological (RCP/ECMP) criteria to diagnose and classify the myeloproliferative neoplasms (MPNs). The crude WHO criteria still miss the masked and early stages of ET and PV. Bone marrow histology has a near to 100% sensitivity and specificity to distinguish thrombocythemia in BCR/ABL positive CML and ET, and the myelodysplastic syndromes in RARS-T and 5q-minus syndrome from BCR/ABL negative thrombocythemias in myeloproliferative disorders (MPD). The presence of JAK2V617F mutation with increased erythrocytes above 6x1012/L and hematocrit (>0.51 males and >0.48 females) is diagnostic for PV obviating the need of red cell mass measurement. About half of WHO defined ET and PMF and 95% of PV patients are JAK2V617F positive. The combination of molecular marker screening JAK2V617F, JAK2 exon 12, MPL515 and CALR mutations and bone marrow pathology is 100% sensitive and specific for the diagnosis of latent, early and classical ECMP defined MPNs. The translation of WHO defined ET, PV and PMF into ECMP criteria have include the platelet count above 350 x109/l, mutation screening and bone marrow histology as inclusion criteria for thrombocythemia in various MPNs. According to ECMP criteria, ET comprises three distinct phenotypes of true ET, ET with features of early (“forme fruste” PV), and ET with a hypercellular erythrocythemic, megakaryocytic granulocytic myeloproliferation (EMGM or masked PV). The ECMP criteria clearly differentiate early erythrocythemic, prodromal and classical PV from congenital polycythemia and idiopathic or secondary erythrocytosis. The burden of JAK2V617F mutation in heterozygous ET and in homozygous PV is of major clinical and prognostic significance. JAK2 wild type MPL515 mutated normocellular ET and MF lack PV features in blood and bone marrow. JAK2/MPL wild type hypercellular ET associated with primary megakaryocytic granulocytic myeloproliferation (PMGM) is the third distinct CALR mutated MPN. The translation of WHO into ECMP criteria for the classification of MPNs have a major impact on prognosis assessment and best choice for first line non-leukemogenic approach to postpone potential leukemogenic myelopsuppressive agents as long as possible in ET, PV and PMGM patients.

Read Full Article HTML DOI: 10.29328/journal.ijbmr.1001004 Cite this Article Read Full Article PDF

Keywords:

Myeloproliferative disorders; Essential thrombocythemia; Polycythemia vera; Chronic idiopathic myelofibrosis; JAK2 V617F mutation; Bone marrow pathology

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