A revised model in mouse and human assumes preferential MK lineage commitment and differentiation through a pathway beginning from HSC and passing MK-P in the presence of TPO/Mpl signaling.23,23 In contrast, ME-Ps likely contribute to erythrocyte production.25 During megakaryopoiesis and erythropoiesis, TPO/Mpl signaling controls expression of the transcriptional factors Friend leukemia virus integration 1 (FLI1) and Kruppel-like factor 1 (KLF1), downstream of c-Mpl, which in turn regulates the individual blood cell types.25 On the other hand, a recent new mechanism of platelet release from MKs by IL-1α and TPO demonstrated that an excess of TPO during platelet biogenesis appears to inhibit platelet release.49