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Jan Jacques Michiels, Vasily Shuvaev, Adrian Trifan, Zwi Berneman, Wilfried Schroyens, Hendrik De Raeve,King Lam, Achille Pich, Vincent Potters, Francisca Valster, Yonggoo Kim, Myungshin Kim
International Hematology and Bloodcoagulation Research Center, Goodheart Institute and Foundation in Nature Medicine, and International Collaboration and Research on Myeloproliferative Neoplasms: ICAR.MPN, Rotterdam, The Netherlands Hematology Clinic in Russian Research Institute of Hematology and Transfusiology, Saint-Petersburg, Russia Department of Medical Genetics, â??Luliu Hatieganuâ?, University of Medicine and Pharmacy, and Department of Genetics, â??Ion Chiricutaâ?Cancer Institute, Cluj-Napoca, Romania Department of Hematology, University Hospital Antwerp, Edegem, Belgium Departments of Pathology, OLV Hospital Aalst and University Hospital Brussels, Belgium Department of Pathology, Erasmus University Medical Center EUMC, Rotterdam, The Netherlands Department of Pathology and Hematology, Bravis Hospital, Bergen op Zoom, The Netherlands Department of Molecular Biotechnology and Health Sciences, Section of Pathology, University of Turin Department of Laboratory Medicine, College of Medicine, The Catholic University of Korea Catholic Genetic Laboratory Center, Seoul St. Maryâ??s Hospital, College of Medicine, The Catholic University of Korea
Posters & Accepted Abstracts: J Blood Disord Treat
The JAK2V617F mutated trilinear myeloproliferative neoplasms (MPN) is featured by clinical phenotypes ranging from essential thrombocythemia (ET), prodromal polycythemia vera (PV), erythrocythemic PV, classical PV, masked PV and PV complicated by splenomegaly and myelofibrosis (MF). The JAK2V617F mutation load increases from below 30% in ET to above 50% in PV and further increases to 80% to 100% due to mitotic recombination of chromosome 9p from heterozygous into heterozygous homozygous and homozygous (9p loss of heterogeneity: 9pLOH) in PV and MF. Bone marrow histology of clustered increase of large pleomorphic megakaryocytes (M) with hyperlobulated nuclei are similar in JAK2V617F normocellular ET, prodromal PV and classical PV. Bone marrow cellularity sequentially increases in JAK2V617F mutated ET and PV due to erythromegakaryoytic (EM) and trilinear erythron-megakaryo-granulocytic (EMG) proliferation.
Two main variants of megakaryocytic leukemia (Dameshek 1951) or ET with platelet counts around 1000x109/L and no features of PV include MPL515 and CALR mutated thrombocythemia. Bone marrow histology in MPL515 thrombocythemia is featured by megakaryocytic myeloproliferation (M) of large to giant megakaryocytes with hyperlobulated staghorn like nuclei in a normocellular bone marrow. Bone marrow histology of CALR thrombocythemia is characterized by megakaryocytic (M) myeloproliferation of large to giant immature megakaryocytes in a normocellular bone marrow followed by primary dual megakaryocytic granulocytic myeloproliferation (PMGM). Natural history and life expectancy of JAK2V617F, MPL515 and CALR mutated MPN patients are related to the response to treatment, the degree of anemia, splenomegaly, myelofibrosis and constitutional symptoms. Epigenetic mutations at increasing age predict unfavorable outcome in adanced stages of JAK2V617F, CALR and MPL mutated MPN. Low dose aspirin in JAK2V617F, MPL515 and TPO mutated ET and phlebotomy on top of aspirin in prodromal and classical PV will prevent platelet-mediated microvascular and major thrombotic events (Sticky Platelet Syndrome). Pegaylated interferon (IFN) in JAK2V617F ET and PV and IFN or anagrelide in CALR and MPL515 mutated thrombocythemias without features of PV are first line treatment options for the control of platelet count to prevent thrombohemorrhagic complications and for the control of MPN disease burden and spleen size to improve survival and quality of life. Ruxolitinib deserves a better place in the treatment of hypercellular PV to reduce MPN disease burden in symptomatic hypercellular PV before significant marrow fibrosis and splenomegaly do occur.
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