By developing a megakaryocyte lineage-specific JAK2V617F knock-in mouse, obtained by crossing a conditional JAK2V617F knock-in mouse with Pf4-Cre transgenic mice, Woods et al. demonstrated that JAK2-mutant MK (i) interact with the wild-type hematopoietic milieu to both initiate and sustain MPN; (ii) induce myeloerythroid expansion resulting in a strong PV-like phenotype; and (iii) produce elevated circulating levels of pro-inflammatory cytokines/chemokines, namely, IL-6, C-C motif ligand (CCL)11, C-X-C motif ligand (CXCL)1, and CXCL2 [52]. Here, JAK2 is linked to acquired polycythemia vera.