Published online Aug 6, 2015. doi: 10.5315/wjh.v4.i3.16
Peer-review started: June 23, 2014
First decision: August 14, 2014
Revised: March 14, 2015
Accepted: April 28, 2015
Article in press: April 30, 2015
Published online: August 6, 2015
The BCR/ABL fusion gene or the Ph1-chromosome in the t(9;22)(q34;q11) exerts a high tyrokinase acticity, which is the cause of chronic myeloid leukemia (CML). The 1990 Hannover Bone Marrow Classification separated CML from the myeloproliferative disorders essential thrombocythemia (ET), polycythemia vera (PV) and chronic megakaryocytic granulocytic myeloproliferation (CMGM). The 2006-2008 European Clinical Molecular and Pathological (ECMP) criteria discovered 3 variants of thrombocythemia: ET with features of PV (prodromal PV), “true” ET and ET associated with CMGM. The 2008 World Health Organization (WHO)-ECMP and 2014 WHO-CMP classifications defined three phenotypes of JAK2V617F mutated ET: normocellular ET (WHO-ET), hypercelluar ET due to increased erythropoiesis (prodromal PV) and ET with hypercellular megakaryocytic-granulocytic myeloproliferation. The JAK2V617F mutation load in heterozygous WHO-ET is low and associated with normal life expectance. The hetero/homozygous JAK2V617F mutation load in PV and myelofibrosis is related to myeloproliferative neoplasm (MPN) disease burden in terms of symptomatic splenomegaly, constitutional symptoms, bone marrow hypercellularity and myelofibrosis. JAK2 exon 12 mutated MPN presents as idiopathic eryhrocythemia and early stage PV. According to 2014 WHO-CMP criteria JAK2 wild type MPL515 mutated ET is the second distinct thrombocythemia featured by clustered giant megakaryocytes with hyperlobulated stag-horn-like nuclei, in a normocellular bone marrow consistent with the diagnosis of “true” ET. JAK2/MPL wild type, calreticulin mutated hypercellular ET appears to be the third distinct thrombocythemia characterized by clustered larged immature dysmorphic megakaryocytes and bulky (bulbous) hyperchromatic nuclei consistent with CMGM or primary megakaryocytic granulocytic myeloproliferation.
Core tip: The 2015 World Health Organization-Clinical Molecular and Pathological criteria define three phenotypes of JAK2V617F mutated myeloproliferative neoplasms (MPNs) essential thrombocythemia (ET), prodromal polycythemia vera (PV), prodromal PV, hypercellular megakaryocytic-granulocytic myeloproliferation and classical PV vs the JAK2 exon 12 mutated idiopathic eryhrocythemia and PV. MPL515 mutated JAK2 wild type ET and myelofibrosis is a distinct thrombocythemia without features of PV in blood and bone marrow. Calreticulin mutated JAK2/MPL wild type ET and myelofibrosis is the third thrombocythemia entity with characteristic features of primary megakaryocytic granulocytic myeloproliferation in the bone marrow, which are not seen in JAK2 and MPL mutated MPNs. MPN disease burden is best reflected by the degree of anemia and splenomegaly on top of mutation allele burden, bone marrow cellularity and increase of reticulin fibrosis.