TPO is a 68-85kD glycoprotein that significantly expands bone marrow and splenic megakaryocytes and their CD34+ precursors, resulting in increased platelet production. TPO supports early megakaryocyte-progenitor colony formation and induces expression of megakaryocyte differentiation markers, polyploidization, and maturation into platelets. Encoded by the proto-oncogene c-Mpl, the TPO receptor c-Mpl lacks intrinsic kinase domains but TPO binding characteristically induces tyrosine phosphorylation of multiple intracellular proteins. The Janus family of non-receptor protein tyrosine kinases (JAKs) is the key mediator of TPO receptor signaling. The N-terminal first 153 amino acids of TPO contains the entire receptor-binding region, while its C-terminal domain has multi-N-linked glycosylation sites and functions to promote TPO secretion and prolong its circulatory survival. TPO affects the entire thrombopoietic process and has stronger effects in the later stages. Other thrombopoietic cytokines include stem cell factor (SCF), IL-3, IL-6, and IL-11. There is great therapeutic potential for TPO for the treatment of many clinical conditions that result in thrombocytopenia. Human, mouse and dog TPO show 69-75% amino acid homology. Recombinant Human TPO ACF is a non-glycosylated protein, containing the 174 amino acids of the receptor binding domain, with a molecular weight of 18.6 kDa (2-5).