Fig. 2. Different models of clonal evolution in Myeloproliferative Neoplasms.

The classical model of mutation acquisition in cancer (left panel) corresponds to the linear and sequential acquisition of mutations one after the other in sub-clones derived from each other. However, several studies of MPN clonal architecture found more complex paths of clonal evolutions. The driver mutation (in red) may be acquired first (center panel), followed by the acquisition of additional mutations in a branching evolution defining clones that diverge at several steps [17, 39, 40, 53]. Alternatively, the driver mutation may be acquired in a preleukemic clone that already carries a mutation in genes such as TET2, DNMT3A or genes of the spliceosome (right panel) [19].