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Jan Jacques Michiels

Jan Jacques Michiels

University Hospitals Antwerp, Netherlands

Title: Clinical, Laboratory, Molecular and Pathobiological (CLMP) criteria for diagnosis of the Myeloproliferative Neoplasms JAK2V617F trilinear polycythemia vera (PV), JAK2 exon 12 PV and JAK2V617F, CALR or MPL mutated thrombocythemias and myelofibrosis


Biography: Jan Jacques Michiels


The JAK2 V617F mutated trilinear myeloproliferative neoplasms (MPN) include a broad spectrum of clinical laboratory and bone marrow features in essential thrombocythemia (ET), prodromal polycythemia vera (PV) and erythrocythemic PV, classical PV and advanced stages of masked PV and PV complicated by splenomegaly and secondary myelofibrosis (MF). Heterozygous JAK2 V617F mutated ET is associated with low JAK2 allele and MPN disease burden and normal life expectance. In combined heterozygous and homozygous or homozygous JAK2 V617F mutated trilinear MPN, the JAK2 mutation load increases from less than 50% in prodromal and early stage PV to above 50% up to 100%in classical PV, advanced PV and PV with MF. Bone marrow histology of megakaryocytes with various degrees of of eryhrocytic, megakaryocytic and granulocytic (EMG) myeloproliferation in JAK2 V617F mutated trilinear MPN clearly differ from monolinear megakaryocytic (M) or dual megakaryocytic granulocytic (MG) myeloproliferation in MPL or calreticulin (CALR) mutated thrombocythemia without features of PV. The morphology of clustered large pleomorphic megakaryocytes with hyperlobulated nuclei are similar in JAK2 V67F thrombocythemia, prodromal PV and classical PV patients. Monolinear megakaryocytic (M) myeloproliferation of large to giant megakaryocytes with hyperlobulated staghorn like nuclei is the hallmark of MPL 515 mutated normocellular thrombocythemia. CALR mutated thrombocythemia usually presents with high platelet count around 1000x10 9 /l and normocellular megakaryocytic (M) proliferation of immuture megakaryocytes with socalled cloud-like hyperchromatic nuclei followed

by dual megakaryocytic granulocytic (MG) myeloproliferation followed by various degrees of bone marrow fibrosis. Natural history and life expectancy are related to the degree of anemia, splenomegaly, myelofibrosis, constitutional symptoms. The acquisition of epigenetic mutations at increasing age independently on top of MPN disease burden predict unfavorable outcome in JAK2 V617F , MPL 515 and CALR mutated myeloproliferative neoplasms (MPNs, which mutually exclude each other.