Use of human leukemia-lymphoma cell lines in hematological research: effects of thrombopoietin on human leukemia cell lines.
Use of human leukemia-lymphoma cell lines in hematological research: effects of thrombopoietin on human leukemia cell lines.
复制标题
人类白血病淋巴瘤细胞系在血液学研究中的应用：血小板生成素对人类白血病细胞系的影响。
作者：
H. Drexler;H. Quentmeier
正常和恶性造血（包括巨核细胞生成和血小板生成）由糖蛋白家族，造血生长因子（细胞因子）调节。孤儿细胞因子受体MPL的鉴定导致血小板产生的主要调节因子的克隆，称为血小板生成素（TPO）。TPO促进巨核祖细胞的增殖和它们分化成产生血小板的巨核细胞。在原代和培养的白血病细胞中也检测了这种新的细胞因子配体-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表达主要发生在具有红-巨核细胞表型的细胞系中。MPL受体也在大部分的原发性急性髓细胞白血病（AML）病例中发现。MPL的表达并不局限于某些形态学亚型，虽然最高的百分比被认为是在红细胞和巨核细胞亚类。一个显着的部分AML病例和红细胞，巨核细胞和髓系白血病细胞系共表达TPO和MPL和mRNA转录，虽然没有生物活性的TPO似乎是由这些细胞分泌。重组TPO明显诱导了相当大比例的原发性AML病例的体外增殖，主要是巨核细胞亚型。TPO显著增强了对GM-CSF、IL-3或SCF有反应的病例中相当大一部分AML细胞的苦参碱诱导的生长。虽然30种生长因子非依赖性红-巨核细胞白血病细胞系均未对TPO产生增殖增加的反应，但TPO强烈增强了几种组成型嘌呤依赖性细胞系（HU-3、M-07 e、M-MOK、OCI-AML-1、TF-1）的生长，这些细胞系可成为TPO依赖性细胞并用作生物测定。无论是在原代细胞，也没有在细胞系TPO出现诱导形态，功能或免疫分化。MPL受体的表达与TPO的增殖反应无关。本文综述的数据记录了MPL受体在髓性白血病细胞上的广泛表达，并且还表明对某些白血病细胞的一些增殖作用，显然对非巨核细胞白血病细胞以及TPO响应细胞系是进一步（病理）生理分析的有力工具。
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.