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.
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.
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.
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.