Drexler H G, Quentmeier H
German Collection of Microorganisms & Cell Cultures, Department of Human and Animal Cell Cultures, Braunschwieg, Germany.
Hum Cell. 1996 Dec;9(4):309-16.
Normal and malignant hematopoiesis (including megakaryocytopoiesis and thrombopoiesis) is regulated by a family of glycoproteins, the hematopoietic growth factors (cytokines). The identification of the orphan cytokine receptor MPL led to the cloning of the primary regulator of platelet production, termed thrombopoietin (TPO). TPO promotes both the proliferation of megakaryocytic progenitor cells and their differentiation into platelet-producing megakaryocytes. Expression and function of this new cytokine ligand-receptor pair were also examined in primary and cultured leukemia cells. Among the large panel of human leukemia cell lines studied, MPL expression occurred predominantly in lines with erythro-megakaryocytic phenotypes. The MPL receptor was also found in a large percentage of primary acute myeloid leukemia (AML) cases. MPL expression was not limited to certain morphological subtypes, although the highest percentages were seen in the erythroid and megakaryocytic subclasses. A significant portion of AML cases and of erythroid, megakaryocytic and myeloid leukemia cell lines co-expressed TPO and MPL and mRNA transcripts, although no biologically active TPO appeared to be secreted by these cells. Recombinant TPO induced clearly in vitro proliferation of a significant percentage of primary AML cases, predominantly of the megakaryocytic subtype. TPO significantly enhanced the cytokine-induced growth of AML cells in a substantial fraction of cases responsive to GM-CSF, IL-3, or SCF. While none of 30 growth factor-independent erythro-megakaryocytic leukemia cell lines responded to TPO with increased proliferation, TPO strongly augmented the growth of several constitutively cytokine-dependent cell lines (HU-3, M-07e, M-MOK, OCI-AML-1, TF-1) which can be made TPO-dependent and used as bioassays. Neither in primary cells nor in cell lines did TPO appear to induce morphological, functional or immunological differentiation. Expression of the MPL receptor is not correlated with a proliferative response to TPO. The data reviewed here document the wide expression of the MPL receptor on myeloid leukemia cells and also suggest some proliferative effects on certain leukemia cells, apparently on non-megakaryocytic leukemia cells as well TPO-responsive cell lines represent powerful tools for further (patho-)physiological analyses.
正常和恶性造血（包括巨核细胞生成和血小板生成）受一族糖蛋白即造血生长因子（细胞因子）调控。孤儿细胞因子受体MPL的鉴定促使血小板生成主要调节因子——血小板生成素（TPO）的克隆。TPO既能促进巨核细胞祖细胞的增殖，又能促使其分化为产生血小板的巨核细胞。还在原代白血病细胞和培养的白血病细胞中检测了这一新的细胞因子配体 - 受体对的表达和功能。在所研究的大量人类白血病细胞系中，MPL表达主要出现在具有红系 - 巨核细胞表型的细胞系中。在很大比例的原发性急性髓系白血病（AML）病例中也发现了MPL受体。MPL表达不限于某些形态学亚型，尽管在红系和巨核细胞亚类中比例最高。相当一部分AML病例以及红系、巨核细胞系和髓系白血病细胞系共表达TPO和MPL以及mRNA转录本，尽管这些细胞似乎未分泌有生物活性的TPO。重组TPO在体外能明显诱导相当比例的原发性AML病例增殖，主要是巨核细胞亚型。在相当一部分对GM - CSF、IL - 3或SCF有反应的病例中，TPO显著增强细胞因子诱导的AML细胞生长。虽然30个不依赖生长因子的红系 - 巨核细胞白血病细胞系中没有一个对TPO有增殖反应增强，但TPO强烈增强了几种组成性依赖细胞因子的细胞系（HU - 3、M - 07e、M - MOK、OCI - AML - 1、TF - 1）的生长，这些细胞系可被诱导依赖TPO并用作生物测定。无论是在原代细胞还是细胞系中，TPO似乎都不会诱导形态、功能或免疫分化。MPL受体的表达与对TPO的增殖反应无关。此处综述的数据证明了MPL受体在髓系白血病细胞上广泛表达，也提示了对某些白血病细胞有一些增殖作用，显然对非巨核细胞白血病细胞也有作用，TPO反应性细胞系是进一步进行（病理 - ）生理分析的有力工具。
