[Mpl ligand (thrombopoietin) and platelet regulation].
After 35 years of research, the physiological regulator of platelet production has been isolated and its gene cloned. This discovery originates from studies performed with the myeloproliferative leukemia virus (MPLV), a murine retrovirus which induces an acute myeloproliferative syndrome in adult mice. MPLV carries in its genome the v-mpl oncogene which corresponds to a truncated form the c-mpl proto-oncogene. c-mpl encodes a cytokine receptor (Mpl-R) belonging to the hematopoietin receptor superfamily. Among the hematopoietic cell lineages, Mpl-R is preferentially expressed on late megakaryocyte progenitors, megakaryocytes and platelets. The ligand for Mpl-R, called Mpl-L or TPO or MGDF or megapoietin, is a glycosylated hormone of 352 amino acids in human which comprises two domains: the N-terminus domain shares 50% similarity with erythropoietin and is responsible for the biological activity; the C-terminus part is required for secretion. Notwithstanding its major action on megakaryocytopoiesis and thrombocytopoiesis, Mpl-L also potentiates the action of other cytokines on several hematopoietic lineages. Mpl-L/TPO/MGDF, the homeostatic regulator of platelet production, might be a useful therapeutical cytokine to treat thrombocytopenia induced in patients by chemotherapy.
Wendling
F
F
INSERM U362, Institut Gustave-Roussy, Villejuif.
Cohen-Solal
K
K
Debili
N
N
Villeval
J L
JL
Titeux
M
M
Vainchenker
W
W
D000818:Animals; D004285:Dogs; D051379:Mice; D010976:Platelet Count; D000090063:Proto-Oncogene Mas; D011817:Rabbits; D013921:Thrombocytopenia / Q000188:drug therapy; D013926:Thrombopoietin / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism / Q000627:therapeutic use
C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D013926:Thrombopoietin