MPL and myeloproliferative disorder: Finally, our data are consistent with the observation that in bone marrow reconstitution studies with cells ectopically expressing Mpl-W515A, an active version found in human MPN, Mpl-Y599F co-mutation prevented development of MPN, while Mpl-Y565F exacerbated disease [25], and extend these observations to otherwise wild-type receptors expressed at endogenously regulated levels in the context of Jak2 and hCalr mutant MPN.