Archives of General Internal Medicine

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The 2001-2016 World Health Organization vs. European clinical, molecular and pathological and the 2008-2018 clinical, laboratories, molecular and pathological (CLMP): Euro-Asian classification of JAK2, CALR and MPL mutated myeloproliferative neoplasms

Joint Event on International Conference on Internal Medicine & Practice and Primary Care & International Meeting on Breast Pathology & Cancer Diagnosis
April 04-05, 2018 | Miami, USA

Jan Jacques Michiels

Antwerp University Hospital, Netherlands

Posters & Accepted Abstracts : Arch Gen Intern Med


The 2008 World Health Organization (WHO) criteria do not define the prodromal and advanced or masked stages of the myeloproliferative neoplasms (MPN) essential thrombocythemia (ET) and polycythemia vera (PV). Bone marrow biopsy (BMB) has a near to 100% sensitivity and specificity to distinguish thrombocythemia in BCR/ABL positive CML and ET, and the myelodysplastic syndromes in RARS-T and 5q-minus syndrome from thrombocythemia in myeloproliferative disorders (MPD). Bone marrow pathology combined with JAK2, MPL and JAK2 exon 12 mutation detection is a pathognomonic clue to each of the MPNs. Each of the JAK2 trilinear MPN markers including spontaneous endogenous erythroid colony (EEC) formation, low serum erythropoietin (EPO) levels, and JAK2 mutations are specific but not sensitive enough to distinguish ET and PV. The combination of JAK2 mutation and increased erythrocytes (>6x109/L), haematocrit (>0.51 males and >0.48 females) is diagnostic for PV (specificity 100%, sensitivity 95%) obviates the need of red cell mass measurement. About half of WHOdefined ET and MF patients are JAK2 positive. According to 2008 ECMP criteria, JAK2 mutated ET comprises three distinct phenotypes of normocellular ET, ET with increased bone marrow erythropoiesis and hyper cellular ET with megakaryocytic granulocytic myeloproliferative without leukoerythroblastosis. Low vs. high JAK2 allele and MPN disease burden in heterozygous ET vs. homozygous PV is of major clinical and prognostic significance. JAK2 wild type MPL mutated normocellular ET is the second distinct MPN. JAK2/MPL wild type hypercellular ET with primary megakaryocytic granulocytic myeloproliferative (PMGM) is the third distinct MPN. CALR mutated ET and MF lack PV features in blood and bone marrow. Pre-treatment bone marrow histology distinguishes JAK mutated trilinear MPN from calreticulin (CALR) and MPL mutated MPN. Increase of clustered large pleomorphic megakaryocytes with hyper lobulated nuclei is similar in JAK ET and PV patients. CALR mutated thrombocythemia shows characteristic bone marrow features of primary dual megakaryocytic granulocytic myeloproliferative (PMGM) without features of PV. MPL mutated thrombocythemia is featured by large to giant megakaryocytes with hyper lobulated stag horn like nuclei in a normocellular bone marrow without features of PV. Increase of JAK2, CALR and MPL MPN disease burden is related the degree of splenomegaly, myelofibrosis and constitutional symptoms during life-long follow-up. The presence of epigenetic mutations at increasing age predict unfavorable outcome in JAK2, CALR and MPL mutated MPNs. Low dose aspirin in ET and phlebotomy on top of aspirin in PV is mandatory to prevent plateletmediated microvascular circulation disturbances. Pegylated interferon is the first line myeloreductive treatment option in prodromal and early stage JAK2 mutated PV and in CALR and MPL mutated thrombocythemia. Low dose pegylated interferon in symptomatic is the first myeloreductive treatment of choice to postpone or eliminate the use of hydroxyurea as long as possible. e:


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