About Us

Henry Publishing Group is an open access, multidisciplinary, international online publishing house, where it promotes publishing of the latest research in the fields of science. The Henry Publishing Group publishes all types of articles like research, reviews, short communication, case reports, mini review, opinion, commentaries, theory, editorials etc., to disseminate the knowledge globally. The article quality is standardized by the strictly blinded peer review process. Henry Publishing Group has been disciplined into Clinical, Medical and Life Sciences. The researchers unveil the laws of nature to the society by research. Henry Publishing Group intensifies sharing of knowledge to the scientific community and helps for the betterment of society. This lays the best forum for scientists, researchers, surgeons, physicians and pedagogy to communicate strengthen and expands the integrity of original research, also assists for the professional development.


Change of the 2008/2016 WHO Criteria into European Clinical, Laboratory Molecular and Pathological (ECMP/CLMP) Classification of BRC/ABL Negative Myeloproliferative Neoplasms Caused by JAK2, MPL and CALR Driver Mutations

Review Article

Change of the 2008/2016 WHO Criteria into European Clinical, Laboratory Molecular and Pathological (ECMP/CLMP) Classification of BRC/ABL Negative Myeloproliferative Neoplasms Caused by JAK2, MPL and CALR Driver Mutations 

 


Jan Jacques Michiels1,9*, Timothy Devos2, Rik Schot3, Francisca Valster4, Vincent Potters5, Katrien Schelfout5, Jiri Schwarz6, Miroslav Penka7, Achille Pich8, Peter Te Boekhorst9, King Lam9 and Hendrik De Raeve10

1Jan Jacques Michiels, Internist Hematologist Goodheart Institute in Nature Medicine & Health, Erasmus Tower, Veenmos 13, 3069 AT Rotterdam, The Netherlands
2Timothy Devos, Internist Hematologist, Department of Hematology, University Hospital Leuven, Gasthuisberg Herenstraat 49, B-3000 Leuven, Belgium
3Rik Schot, Internist Hematologist, Department of Hematology, University Hospital Brussels, Laarbeeklaan 101, B-1090, Brussels, Belgium
4Fransje Valster, Internist Hematologist, Department of Internal Medicine, BRAVIS Hospital, Boerhaaveplein 1, 4624 VT, Bergen op Zoom, The Netherlands
5Vincent Potters, Pathologist, Department of Pathology, BRAVIS Hospital, Boerhaveplein 1, 4624 VT, Bergen op Zoom, The Netherlands
6Katrien Schelfout, Pathologist, Department of Pathology, BRAVIS Hospital, Boerhaveplein 1, 4624 VT, Bergen op Zoom, The Netherlands
7Jiri Schwarz and Miroslav Penka, Czech National Working Group on Myeloproliferative Disorders/ Myeloproliferative Neoplasms (MPD/MPN) of the Czech Hematology Society, The Czech Republic
8Achille Pich Department of Molecular Biotechnology and Health, Section Pathology, University of Turin, Italy
9Peter Te Boekhorst and King Lam, Department of Hematology, Erasmus Medical Center, Erasmus Univerisity Rotterdam , Dr Molewaterplein 40, 3015 GD Rotterdam, The Netherlands
10Hendrik De Raeve, Pathologist, Department of Pathology OLV Hospital Aalst OLV Ziekenhuis,Moorselbaan 164, B-9300 Aalst, Belgium and University Medical Center Brussels, Laarbeeklaan 101, B-1090, Brussels, Belgium

*Corresponding author: Jan Jacques Michiels, Internist Hematologist Goodheart Institute in Nature Medicine & Health, Erasmus Tower, Veenmos 13, 3069 AT Rotterdam, The Netherlands, Tel: +316 26970534; E-mail: goodheartcenter@outlook.com

Received: October 29, 2019; Accepted: December 12, 2019; Published: December 27, 2019

Abstract

Ninety five percent of Polycythemia Vera (PV) patients and half of patients with Essential Thrombocythemia (ET) patients have low serum Erythropoietin (EPO) levels, and carry the JAK2V617F mutation. The change of 2008/2016 WHO criteria for ET into the European Clinical, Molecular and Pathologic (ECMP) classification of the JAK2V617F positive ET patients refers to three phenotypes of ET. First, heterozygous JAK2V617F mutated normocellular ET life-long. Second, hypercellular ET due to increased erythropoiesis (prodromal PV) preceding classical PV. Third, hypercellular and ET with erythrocythic-megakaryocytic-granulocytic bone marrow proliferation not meeting the WHO criteria for PV (masked PV). JAK2V617F mutation load is low and stable around 30% in heterozygous normocellular ET but high and increasing from below 50% to 80-100% homozygous JAK2V617F mutated PV and masked PV. JAK2V617F mutation load is related to MPN disease burden in terms of leucocytosis, splenomegaly, constitutional symptoms and myelofibrosis. Five distinct JAK2V617F trilinear MPN stages can be distinguished: JAK2V617F heterozygous positive ET, JAK2V617F homozygous positive PV; benign JAK2exon 12 PV; MPL515 mutated ET without features of PV and CALR mutated ET without features of PV. CALR mutated thrombocythemia  has been recognized and described in great detail by Georgii & Michiels between 1990 and 1997 as Primary Megakaryocytic Granulocytic Myeloproliferation (PMGM). 

Bone marrow features in JAK2V617F mutated ET and PV are similar characterized by medium sized to large (pleomorphic) megakaryocytes with hyperlobulated nuclei. Bone marrow histology in MPL515 positive ET show clustered large to giant megakaryocytes with hyperlobulated stag-horn-like nuclei, in a normocellular bone marrow. Bone marrow histology in CALR mutated ET patients is dominated by dense clusters of large immature dysmorphic megakaryocytes with bulky (cloud-like) hyperchromatic nuclei, which are never seen in JAK2V617F , JAK2exon12 and MPL515 mutated MPN. The 2008/2016 WHO defined terminology of ET and PMF can easily be replaced by ECMP defined CALR-, MPL515-and JAK2V617F-mutated thrombocythemia and secondary myelofibrosis (MF) with various degrees of splenomegaly, hypersplenism and myelofibrotic transformation of the bone marrow


Keywords

Bone marrow pathology; Essential thrombocythemia; JAK2 mutation; MPL mutation, calreticulin mutation; Myelofibrosis; Polycythemiavera; Primary megakaryocytic granulocytic myeloproliferation; Reticulin fibrosis

Citation: Michiels JJ, Devos T, Schot R, Valster F, Potters V, et al. (2019) Change of the 2008/2016 WHO Criteria into European Clinical, Laboratory Molecular and Pathological (ECMP/CLMP) Classification of BRC/ABL Negative Myeloproliferative Neoplasms Caused by JAK2, MPL and CALR Driver Mutations. J Hematol Hemother 4: 006.
Copyright: © 2019 Michiels JJ, 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.

jn-img1