The role of the MPL receptor in myeloproliferative disorders.

Thrombopoietin (TPO) is a primary regulator of megakaryopoiesis and thrombopoiesis, and has recently been identified as the ligand for the cytokine receptor MPL. Several lines of evidence suggest that dysregulation of MPL expression or TPO production are implicated in the pathogenesis of various myeloproliferative disorders. For example, mutations in the MPL gene can cause factor-independent growth and a transformed phenotype in vivo, and MPD may be associated with altered expression of the MPL receptor or TPO. Blast cells from patients with acute myelogenous leukemia (AML) often display MPL, and TPO induces some of these to proliferate. In sum, MPL may play a role as part of an autocrine pathway of MPD. While much remains to be clarified about the therapeutic use of TPO in AML, early results suggest it may be useful for platelet donation and/or priming to alleviate chemotherapy-induced thrombocytopenia in other malignant conditions.