The thrombopoietin/MPL axis is activated in the Gata1^low mouse model of myelofibrosis and is associated with a defective RPS14 signature.

ABSTRACT: Myelofibrosis (MF) is characterized by hyperactivation of thrombopoietin (TPO) signaling, which induces a RPS14 deficiency that de-regulates GATA1 in megakaryocytes by hampering its mRNA translation. As mice carrying the hypomorphic Gata1^low mutation, which reduces the levels of Gata1 mRNA in megakaryocytes, develop MF, we investigated whether the TPO axis is hyperactive in this model. Gata1^low mice contained two times more Tpo mRNA in liver and TPO in plasma than wild-type littermates. Furthermore, Gata1^low LSKs expressed levels of Mpl mRNA (five times greater than normal) and protein (two times lower than normal) similar to those expressed by LSKs from TPO-treated wild-type mice. Gata1^low marrow and spleen contained more JAK2/STAT5 than wild-ty

SUBMITTER: Zingariello M 

PROVIDER: S-EPMC5520398 | biostudies-literature | 2017 Jun

REPOSITORIES: biostudies-literature