International Conference on Oncology & Hematology
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Accepted Abstracts

Translation of the PVSG/WHO classifications into novel Clinical, Laboratory, Molecular and Pathological (2019 CLMP) criteria for distinct myeloproliferative neoplasms caused by JAK2V617F JAK2EXON12, CALR, MPL515 and TPO driver mutations

Jan Jacques Michiels*
Goodheart Institute & Foundation in Nature Medicine, Netherlands

Citation: Michiels JJ (2019) Translation of the PVSG/WHO classifications into novel Clinical, Laboratory, Molecular and Pathological (2019 CLMP) criteria for distinct  myeloproliferative neoplasms caused by JAK2V617F JAK2EXON12, CALR, MPL515 and TPO driver mutations

Received: March 23, 2019         Accepted: March 25, 2019         Published: March 25, 2019

Abstract

The JAK2V617F 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 JAK2V617F mutated ET is associated with low JAK2 allele and MPN disease burden and normal life expectance. The JAK2V617F mutation load in combined heterozygous/ homozygous and homozygous increases from less than 50% in prodromal and classical PV to above 50% up to 100% in advanced PV and PV with MF. The morphology of clustered large pleomorphic megakaryocytes with hyperlobulated nuclei are similar in JAK2V617F ET, prodromal PV and classical PV patients. Bone marrow histology features in JAK2V617F mutated trilinear MPN show pathognomonic diagnostic erythrocytic, megakaryocytic and granulocytic (EMG) proliferation, which clearly differ from monolinear  megakaryocytic (M) in MPL515 mutated ET and dual megakaryocytic granulocytic (MG) myeloproliferation in calreticulin (CALR) mutated thrombocythemia without features of PV. Monolinear megakaryocytic (M) myeloproliferation of large to giant megakaryocytes with hyperlobulated staghorn like nuclei is the hallmark of MPL515 mutated normocellular thrombocythemia. CALR mutated thrombocythemia usually presents with high platelet count around or above 1000x109/l and normocellular megakaryocytic (M) proliferation of immature megakaryocytes with cloud-like hyperchromatic nuclei followed by dual megakaryocytic granulocytic (MG) proliferation with various degrees of bone marrow reticulin and collagen fibrosis. Natural history and life expectancy of MPN patients are related to the response to treatment and the degree of anemia, splenomegaly, myelofibrosis and constitutional symptoms. The acquisition of epigenetic mutations at increasing age on top of MPN disease burden independently predict unfavorable life expectance in advanced stages of JAK2V617F , MPL515 and CALR mutated MPNs.

Keywords: Myeloproliferative neoplasms; Essential thrombocythemia; Polycythemia vera; Primary megakaryocytic granulocytic myeloproliferation; Myelofibrosis; JAK2V617F mutation; MPL515 mutation; Calreticulin mutation; JAK2 wild type; Bone marrow histology