These and other challenges facing JAK inhibitor treatment in myelofibrosis 25 could be explained either by insufficient dosing because of anaemia and thrombocytopenia resulting from inhibition of wild-type (WT) JAK2, by addiction to one pathway downstream of JAK2 that needs very low levels of residual JAK activation, by continuous signalling from other JAKs in heteromeric complexes with the inhibited JAK2 26, or by other genetic events that might drive MPN in addition from JAK pathway. The gene discussed is JAK2; the disease is myeloproliferative disorder.