Here, we compared differentiated, PV patient-specific iPSCs with a homozygous JAK2V617F constitution and gender-matched iPSCs with wild-type JAK2 (JAK2wt), along with genetically modified JAK2V617F-expressing HEL cells and immunohistochemical (IHC) staining of PV patients’ BM, to investigate the hierarchy and consequences of the activated inflammatory signature. The gene discussed is JAK2; the disease is acquired polycythemia vera.