Enver T, Zhang J W, Anagnou N P, Stamatoyannopoulos G, Papayannopoulou T
Division of Medical Genetics, University of Washington, Seattle 98195.
Mol Cell Biol. 1988 Nov;8(11):4917-26. doi: 10.1128/mcb.8.11.4917-4926.1988.
We investigated the programs of globin gene expression in three known (K562, HEL, and KMOE) and three novel (OCI-M1, OCI-M2, and HEL-R) human erythroleukemic cell lines of adult origin. RNAs from induced and uninduced cells were analyzed for epsilon-, gamma-, delta-, and beta-, zeta-globin-specific transcripts. While high-level gamma-globin expression was common, the lines differed in their expression of embryonic (epsilon, zeta) and adult (delta, beta) globin mRNAs. The patterns of globin gene methylation were generally consistent with their observed expression profiles, with many of the same correlations being seen in normal cells. Although the programs of globin gene expression and methylation displayed by the lines appeared to be diverse, they were not random; rather, they made developmental sense, mimicking defined globin gene programs observed during normal human development. The characteristics exhibited by several of these lines suggest that they may have been derived from the transformation of multi- or oligopotent hematopoietic progenitor cells. We speculate that the expression of fetal or embryonic globins in these adult erythroleukemic cell lines is not an aberration of neoplastic transformation but is indicative of a fetal or embryonic potential in normal adult hematopoietic progenitors.
我们研究了源自成人的三种已知(K562、HEL和KMOE)以及三种新型(OCI-M1、OCI-M2和HEL-R)人红白血病细胞系中的珠蛋白基因表达程序。对诱导和未诱导细胞的RNA进行分析,检测ε-、γ-、δ-、β-、ζ-珠蛋白特异性转录本。虽然高水平的γ-珠蛋白表达很常见,但这些细胞系在胚胎型(ε、ζ)和成人型(δ、β)珠蛋白mRNA的表达上存在差异。珠蛋白基因甲基化模式总体上与其观察到的表达谱一致,在正常细胞中也可见到许多相同的相关性。尽管这些细胞系所显示的珠蛋白基因表达和甲基化程序似乎多种多样,但并非随机;相反,它们具有发育意义,模仿了正常人类发育过程中观察到的特定珠蛋白基因程序。其中几个细胞系所表现出的特征表明,它们可能源自多能或寡能造血祖细胞的转化。我们推测,这些成人红白血病细胞系中胎儿型或胚胎型珠蛋白的表达并非肿瘤转化的异常现象,而是正常成人造血祖细胞具有胎儿或胚胎潜能的指示。