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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 3.

Figure 3

Model of current understanding of genetic events responsible for leukemic transformation of chronic BCR – ABL1 negative myeloproliferative neoplasms (MPNs). Although JAK2 V617F mutations are sufficient for development of MPN phenotype, a large amount of evidence suggests that earlier genetic events predate development of the JAK2 V617F mutations to establish a “pre-leukemic” MPN initiating cell. Mutations in TET2 as well as DNMT3A have been most frequently described as predating JAK2V617F mutations in patients with MPN. Acquisition of the JAK2 V617F mutation then results in overt MPN clinical disease. Later, acquisition of further mutations, either in a cell bearing the JAK2 mutation or a JAK2 wild type cell results in transformation to acute leukemia. Currently, few studies regarding leukemic transformation of CALR-mutant chronic MPN patients have been described.