c-Mpl ligand is a humoral regulator of megakaryocytopoiesis

Abstract

Megakaryocytopoiesis is the cellular developmental process that leads to platelet production. At least two humoral growth factors may be necessary for megakaryocyte proliferation and maturation. One is a megakaryocyte-colony stimulating factor (MK-CSF) which induces the proliferation and differentiation of megakaryocyte progenitors, and the second, thrombopoietin, is a megakaryocyte maturation factor. Neither of these factors has been fully characterized. The proto-oncogene c-mpl, an orphan member of the haematopoietin receptor family, is specifically involved in megakaryocyte regulation. Here we present evidence that the c-mpl-encoded receptor binds a ligand (c-Mpl ligand) which is a humoral factor implicated in platelet homeostasis. Our results suggest that c-Mpl ligand, thrombopoietin and MK-CSF might be the same molecule.

Blood thrombopoietin, IL-6 and IL-11 levels in patients with agnogenic myeloid metaplasia

“…formation, [14][15][16][17] and the formation of fully mature megakaryterized by bone marrow megakaryocyte hyperplasia and clusocytes and functional platelets in liquid culture. 18 Injections of ters of megakaryocytes, in which many of the megakaryocytes recombinant TPO into mice and nonhuman primates increase are atypical.…”

Thrombopoietin, c‐Mpl ligand, induces tyrosine phosphorylation of Tyk2, JAK2, and STAT3, and enhances agonists‐induced aggregation in platelets in vitro

“…Recently, several groups [2][3][4][5] cloned the ligand for the c-Mpl proto-oncogene [6] which is a member of the cytokine receptor superfamily. These studies and others have demonstrated that c-Mpl ligand plays a critical role in megakaryocytopoiesis and thrombopoiesis both in vitro and in vivo [2][3][4][5][7][8][9][10]. Therefore, c-Mpl ligand has been termed thrombopoietin (TPO) [3,7,8] or megakaryocyte growth and development factor (MGDF) [4].…”

“…These studies and others have demonstrated that c-Mpl ligand plays a critical role in megakaryocytopoiesis and thrombopoiesis both in vitro and in vivo [2][3][4][5][7][8][9][10]. Therefore, c-Mpl ligand has been termed thrombopoietin (TPO) [3,7,8] or megakaryocyte growth and development factor (MGDF) [4]. The cytokine receptor superfamily, which lacks a tyrosine kinase domain, couples ligand binding with the induction of protein-tyrosine phosphorylation that is essential for cytokine signaling [11].…”

True

“…[1][2][3] The recently defined ligand for the Mpl receptor, thrombopoietin (TPO), has been found to be the principal regulatory cytokine of megakaryocytopoiesis and thrombopoiesis. [4][5][6][7][8] It appears that TPO is able not only to induce differentiation of megakaryocytic precursors, but also to expand early megakaryocytic progenitors. 9,10 TPO also directly affects more primitive hematopoietic cells, not yet committed towards the megakaryocytic lineage.…”