These data identify altered expression signatures of TGF-β1 signaling that may be responsible for MF in Gata1(low) mice and may represent additional targets for therapeutic intervention in PMF.
Although GATA1 is not mutated in PMF, reduced GATA1 content in megakaryocytes as a consequence of ribosomal deficiency is a hallmark of myelofibrosis (both in humans and mouse models) and, in fact, a driving event in the disease.
Spontaneous remission in 2 children with myelofibrosis, one with megakaryocytic acute myeloblastic leukemia and t(1;22) (with recurrence later) and one with Down syndrome and GATA1 mutation (permanent), are described.
As mice carrying the hypomorphic Gata1<sup>low</sup> mutation, which reduces the levels of Gata1 mRNA in megakaryocytes, develop MF, we investigated whether the TPO axis is hyperactive in this model.