Promotion of megakaryocyte progenitor expansion and differentiation by the c-Mpl ligand thrombopoietin.
The development of blood cells including expansion of megakaryocyte progenitor cells requires the interplay of marrow stromal cells and polypeptide cytokines. Recently, characterization of c-Mpl, the receptor encoded by the proto-oncogene c-mpl, revealed structural homology with the haematopoietic cytokine receptor family, and its involvement in megakaryocyte development. We report here that the ligand for c-Mpl is relatively lineage specific, works both alone and synergistically with early acting cytokines to support megakaryocyte colony formation, and acts at a late stage of development to increase megakaryocyte size, polyploidization and expression of differentiation markers. In vivo, c-Mpl ligand stimulates platelet production by greatly expanding marrow and splenic megakaryocytes and their progenitors, and by shifting the distribution of megakaryocyte ploidy to higher values. Thus, as c-Mpl ligand has the expected characteristics of the major regulator of megakaryocyte development, we propose that it be termed thrombopoietin.
Kaushansky
K
K
Division of Hematology, University of Washington School of Medicine, Seattle 98195.
Lok
S
S
Holly
R D
RD
Broudy
V C
VC
Lin
N
N
Bailey
M C
MC
Forstrom
J W
JW
Buddle
M M
MM
Oort
P J
PJ
Hagen
F S
FS
D000110:Acetylcholinesterase / Q000378:metabolism; D000818:Animals; D000943:Antigens, Differentiation / Q000378:metabolism; D001854:Bone Marrow Cells; D002454:Cell Differentiation; D002460:Cell Line; D006801:Humans; D008024:Ligands; D008533:Megakaryocytes / Q000166:cytology*; D051379:Mice; D009363:Neoplasm Proteins; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins; D018121:Receptors, Cytokine; D011971:Receptors, Immunologic / Q000378:metabolism*; D053628:Receptors, Thrombopoietin; D013154:Spleen / Q000166:cytology; D013926:Thrombopoietin / Q000378:metabolism*
D000943:Antigens, Differentiation; D008024:Ligands; C000715470:MAS1 protein, human; D009363:Neoplasm Proteins; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins; D018121:Receptors, Cytokine; D011971:Receptors, Immunologic; D053628:Receptors, Thrombopoietin; C082218:MPL protein, human; D013926:Thrombopoietin; D000110:Acetylcholinesterase