A clue that genetic alterations that promote the development of MPNs may occur in precursors of the HSC before birth is provided by the observation that infants with Downs Syndrome who accumulate during their fetal life deletions in the GATA1 gene supporting expression only of a hypomorphic isoform of the GATA1 protein are prone to develop a transient MPN, which eventually progresses to acute megakaryocytic leukemia [31,43]. The gene discussed is GATA1; the disease is acute megakaryoblastic leukemia.