Most JAK2 mutations associated with hematological malignancies encode missense mutations that localize within JAK2 exon 12 of SH2L-JH2 linker region, or within JAK2 exons 14 or 16 of the pseudokinase domain, highlighting these regions as oncogenic hot-spots for mutation (Figure 4A) (Mullighan et al., 2009c; Gnanasambandan and Sayeski, 2011; Silvennoinen and Hubbard, 2015b). Here, JAK2 is linked to hematologic disorder.