Published: 01 March, 2019 | Volume 2 - Issue 1 | Pages: 001-017
Upper part. Disease heterogeneity of JAK2V617F myeloproliferative disease according to Villeval, James, Pisani, Casedevall & Vainchenker 2006 . The level and duration of JAK2V617F expression directly contribute to the diversity of trilinear myeloproliferative neoplasms. The JAK2V617F occurs in a hematopoietic stem cell and give rise to the onset of ET and PV. The trilinear MPN progresses from heterozygous ET to hetero/homozygous ET/PV (forme fruste PV) and homozygous JAK2V6167F mutated classical PV through mitotic recombination at chromosome 9p resulting in the loss of heterogeneity (9pLOH)36. A low level of heterozygous JAK2V617F kinase activity is enough to activate the MPL receptor to produce the clinical ET phenotype. A higher level of hetero/homozygous and a high level of homozygous JAK2V617F kinase activity is needed to activate the EPOR, MPL and G-CSFR receptors to produce an ET/PV (forme fruste PV), overt classical PV and advanced masked PV [32,33,36]. Lower part. Dynamics of the JAK2V617F mutated trilinear MPN disease including the sequential evolution of ET, forme fruste PV (prodromal PV), classical PV and advanced PV complicated by post-PV myeloid metaplasia of the spleen and secondary myelofibrosis according to ECP and ECMP classifications of the Myeloproliferative Neoplasms (MPN) designed by Michiels & Thiele [16,34,35,47-50].