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. Author manuscript; available in PMC: 2016 Oct 24.
Published in final edited form as: Leuk Lymphoma. 2014 Nov 19;56(7):1938–1948. doi: 10.3109/10428194.2014.974594

Figure 2.

Figure 2

Proposed pathophysiology of the BCR – ABL1 negative classic myeloproliferative neoplasms (MPNs) based on new genetic insights. In this model, proposed by Mario Cazzola and Robert Kralovics, all MPNs originate in a state most consistent with essential thrombocythemia (ET). This occurs in patients with heterozygous JAK2 V617F mutations, CALR mutations or MPL mutations. Patients with heterozygous JAK2 V617F mutations that undergo copy neutral loss-of-heterozygosity (CN-LOH) of the locus of the JAK2 V617F mutation (on chromosome 9p) undergo a phenotypic switch from an ET phenotype to a phenotype most consistent with polycythemia vera (PV). Further genetic and/or epigenetic alterations may then result in further evolution from PV to myelofibrosis (MF). In contrast, patients with a MPL or CALR mutation either remain with a phenotype consistent with ET or undergo evolution directly to MF. Genetic alterations known to be associated with transition from ET to MF include CN-LOH of the locus of MPL mutation (on chromosome 1p). Additionally, genetic data suggest that progressive expansion of CALR mutant clones is associated with transformation from ET to MF.