PROMOTION OF MEGAKARYOCYTE PROGENITOR EXPANSION AND DIFFERENTIATION BY THE C-MPL LIGAND THROMBOPOIETIN

被引：940

作者：

KAUSHANSKY, K ^{[1
]}

LOK, S ^{[1
]}

HOLLY, RD ^{[1
]}

BROUDY, VC ^{[1
]}

LIN, N ^{[1
]}

BAILEY, MC ^{[1
]}

FORSTROM, JW ^{[1
]}

BUDDLE, MM ^{[1
]}

OORT, PJ ^{[1
]}

HAGEN, FS ^{[1
]}

ROTH, GJ ^{[1
]}

PAPAYANNOPOULOU, T ^{[1
]}

FOSTER, DC ^{[1
]}

机构：

[1] ZYMOGENET INC,SEATTLE,WA 98105

来源：

NATURE | 1994年 / 369卷 / 6481期

关键词：

D O I：

10.1038/369568a0

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

THE development of blood cells including expansion of megakaryocyte progenitor cells requires the interplay of marrow stromal cells and polypeptide cytokines(1-10). Recently, characterization of c-Mpl, the receptor encoded by the proto-oncogene c-mpl, revealed structural homology with the haematopoietic cytokine receptor family(11), and its involvement in megakaryocyte development(12). We report here that the ligand for c-Mpl(13) 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.

引用

页码：568 / 571

页数：4

共 28 条

[1] SELECTIVE GROWTH-RESPONSE TO IL-3 OF A HUMAN-LEUKEMIC CELL-LINE WITH MEGAKARYOBLASTIC FEATURES [J].