Abstract

In this critical appraisal of the literature Michiels and De Raeve incorporated the 2007/2008 WHO classification into the European Clinical Molecular and athological (2008 ECMP 2020 CLMP) criteria by including bone marrow biopsy as a pathognomonic clue with a 100% sensitivity and specificity. The 2008 ECMP classification distinguish the BCR/ABL-negative Myeloproliferative Disorders/Neoplasms (MPD/MPN) essential thrombocythemia (ET) and polycythemia Vera (PV) and primary megakaryocytic granulocytic myeloproliferation (PMGM) from BCR/ABL positive chronic myeloid leukemia (CML) and ET, and from thrombocythemia associated with myelodysplastic syndromes in RARS-T and 5q-minus syndrome. The megakaryocytes in Ph-positive in BCR/ABL-positive ET and CML are small with mon- or bi-lobulated nuclei whereas the megakaryocytes in BCR/ABL-negative MPD/MPN are increased, clustered and enlarged as compared to controls showing variable degrees hyperlobulated nuclei in JAK2, TPO, MPL mutated and JAK2 wild type MPN. The 2007/2008 WHO criteria overlook the early latent stages of ET and PV and primary myelofibrosis (PMF) is not a disease but a secondary event in all variants of MPD/MPN.

The 2008 ECMP 2020 CLMP criteria distiguish at least six JAK2^V617F mutated MPN stages that have important prognostic and therapeutic implications: normocellular ET, prodromal PV, classical PV, hypercellular PV, EMGM = masked PV, advanced PV with various degrees of myelofibrosis. The combination of spontaneous EEC, increased leukocyte alkaline phospatase score, decreased serum erythropoietin (EPO) and JAK2^V617F mutation is specific for JAK2^V617F mutated ET, prodromal PV, masked PV and classical PV but are normal in JAK2 wild type MPL and CALR mutated ET and MF. MPL⁵¹⁵ mutated thrombocythemia is a separate and distinct MPN entity without features of PV. JAK2/MPL wild type ET associated with PMGM is the third distinct CALR mutated MPN entity. Acetylsalicylic acid (Aspirin) cures platelet mediated erythromelalgia and microvascular disturbances by inhibiting platelet cyclooxygenase. Platelet ADP-receptor inhibitors (ticlopedin, clopidrogrel, ticagrelor) and anticoagulation with vitamine K antagonist (VKA) and direct oral anticoagulants (DOAC) do not relief the aspirin responsive microcirculatory disturbances in JAK2^V617F and MPL⁵¹⁵ mutated ET and PV patients. The ‘Early Interferon Intervention Strategy has become the first line myeloreductive treatment option in early stage ET and PV to postpone or even eliminate hydroxyurea and ruxolitininb during long-term or even lifelong follow-up.

Keywords: Myeloproliferative Neoplasm; Essential Thrombocythemia; Polycythemia Vera; Myelofibrosis; JAK2^V617F Mutation; MPL⁵¹⁵ Mutation; Bone Marrow Pathology; World Health Organisation; European; Classification

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Citation

Citation: Jan Jacques Michiels., et al. “Incorporation of the 2008 WHO into 2008/2020 ECMP/CLMP Classification for Staging and Prognosis Assessment of JAK2, MPL, TPO, MPL and CALR Mutated Myeloproliferative Neoplasms (MPN): From Dameshek to Vainchenker and Michiels 1940 - 2020: A Historical Appraisal and Novel Therapeutic Implications". Acta Scientific Medical Sciences 4.4 (2020): 99-121.

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Copyright: © 2020 Jan Jacques Michiels., et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.