Finally, mutation of Mpl-Y604 resulted in no discernable effect on activation of TPO-dependent signalling pathways; however in MplY604F/Y604F mice, some modest effects were noted such as mild thrombocytosis at steady state, a prolonged response to 5-FU and modest selective enhancement of platelet or megakaryocyte numbers in models of MPN. Here, TPO is linked to thrombocytosis disease.