The c-mpl proto oncogene was first identified as the cellular homolog of the viral oncogene v-mpl in the myeloproliferative leukemia virus (MPLV). However, based on homology with a member of the cytokine receptor superfamily, the c-mpl gene was predicted to encode a receptor for some cytokine. An antisense oligomer against c-mpl selectively inhibited megakaryocytic colony formation. Moreover, c-mpl-deficient mice had selectively dramatic decrease in the number of circulating platelets and megakaryocytes in the spleen and bone marrow. Collectively, these observations suggested that the c-Mpl ligand is identical to thrombopoietin (TPO). Several groups have purified TPO as the c-Mpl ligand. In fact, in vitro and in vivo studies have shown that recombinant TPO alone can support the proliferation and differentiation of megakaryocyte progenitor cells and maturation of megakaryocyte. There are two types of alternatively spliced isoforms of c-mpl, c-mpl-P (wild type) and c-mpl-K (truncated).