Chabot M C, Greene D G, Brockschmidt J K, Capizzi R L, Wykle R L
Department of Medicine, Bowman Gray School of Medicine, Wake Forest University, Winston-Salem, North Carolina 27103.
Cancer Res. 1990 Nov 15;50(22):7174-8.
The glycerolipids of most cells are characterized by a specific proportion of ether linkages at the sn-1 position of the glycerol backbone. A number of tumors are known to have altered concentrations of ether-linked lipids compared to normal tissues. However, no through examination of the ether-lipid content of human leukemia cells has been reported despite the importance of these lipids in normal leukocyte function. In the present study samples were obtained from adults with acute myelogenous leukemia (AML), chronic granulocytic leukemia in blast crisis, and acute lymphocytic leukemia and from healthy human donors. The cellular lipids were extracted, the individual phospholipid classes were isolated, lipid phosphorus content was determined, and the lipids were converted to diglyceride benzoate derivatives for separation and quantitation of the subclasses by high performance liquid chromatography. The data indicate that all the leukemic cells analyzed have an altered phospholipid composition compared to their respective normal leukocytes. Furthermore, among the AML patients both the percentage of the choline-containing phosphoglyceride fraction (PC) which is alkyl linked and the nmoles alkyl-PC/10(6) cells differ significantly by FAB subtype. A positive correlation between the levels of alkyl-PC and the degree of cellular differentiation is observed. Although no differences are observed between chronic granulocytic leukemia in blast crisis and AML lipids, the leukemic cells contain dramatically lower levels of alkyl-linked PC than do normal polymorphonuclear leukocytes. In contrast, no differences are observed between the alkyl-PC content of normal and leukemic lymphocytes. In light of the relations among ether-lipids, protein kinase C, and cell differentiation, these data suggest the ether-linked lipids are important in myeloid cell function and differentiation.
大多数细胞的甘油脂的特征在于甘油主链sn-1位上醚键的特定比例。已知与正常组织相比,许多肿瘤中醚连接脂质的浓度发生了改变。然而,尽管这些脂质在正常白细胞功能中很重要,但尚未有关于人类白血病细胞醚脂含量的全面研究报道。在本研究中,样本取自患有急性髓性白血病(AML)、处于原始细胞危象的慢性粒细胞白血病和急性淋巴细胞白血病的成年人以及健康的人类供体。提取细胞脂质,分离各个磷脂类别,测定脂质磷含量,并将脂质转化为二甘油苯甲酸酯衍生物,通过高效液相色谱法分离和定量亚类。数据表明,与各自的正常白细胞相比,所有分析的白血病细胞的磷脂组成都发生了改变。此外,在AML患者中,含胆碱的磷酸甘油酯部分(PC)中烷基连接的百分比以及每10^6个细胞中烷基-PC的纳摩尔数因FAB亚型而异。观察到烷基-PC水平与细胞分化程度之间呈正相关。虽然在原始细胞危象的慢性粒细胞白血病和AML脂质之间未观察到差异,但白血病细胞中烷基连接的PC水平明显低于正常多形核白细胞。相比之下,正常和白血病淋巴细胞的烷基-PC含量之间未观察到差异。鉴于醚脂、蛋白激酶C和细胞分化之间的关系,这些数据表明醚连接脂质在髓细胞功能和分化中很重要。