Drexler H G, Quentmeier H, MacLeod R A, Uphoff C C, Hu Z B
DSM-German Collection of Microorganisms and Cell Cultures, Department of Human and Animal Cell Cultures, Braunschweig, Germany.
Leuk Res. 1995 Oct;19(10):681-91. doi: 10.1016/0145-2126(95)00036-n.
Acute promyelocytic leukemia (APL) serves as a paradigm in clinical and biological leukemia research. Firstly, APL represents a model for the new therapeutic approach of differentiation therapy, taking advantage of the ability of APL cells to respond to retinoic acid treatment by terminal differentiation. Secondly, the 15;17 chromosomal translocation specific for APL leads at the molecular genetic level to a chimeric gene fusing the PML and RAR alpha genes and appears to be an instrumental, if not actually the causative event, in the neoplastic process. These unique characteristics of an otherwise rather rare disease have recently attracted intense research interest. As in other types of leukemia where continuous cell lines are powerful research tools, studies using APL-derived cell lines have contributed a large body of relevant data in efforts to unravel the pathobiology and leukemogenesis of APL. Three cell lines have been reported to be derived from patients with APL: HL-60, NB-4 and PL-21. Both HL-60 and PL-21 lack t(15;17) while NB-4 carries this cytogenetic hallmark pathognomonic for APL. Morphological and immunophenotypical examinations of the cell lines do not permit a clear assignment to any stage of myelomonocytic differentiation. Some additional data, such as expression of myeloperoxidase, monocyte-specific esterase and annexin VIII, together with the cytogenetic and molecular biological information, suggest that NB-4 is the only genuine promyelocytic leukemia cell line, whereas HL-60 may represent a discrete stage of differentiation between the late myeloblasts and the promyelocyte; PL-21 has distinct features associated with monocytic cells. These cell lines provide unique in vitro model systems for studying the cellular and molecular events involved in the proliferation and differentiation of normal and leukemic myelomonocytic cells.
急性早幼粒细胞白血病（APL）是临床和生物学白血病研究的典范。首先，APL代表了分化疗法这一新型治疗方法的模型，利用APL细胞通过终末分化对维甲酸治疗产生反应的能力。其次，APL特有的有的的15;17染色体易位在分子遗传水平上导致PML和RARα基因融合的嵌合基因，并且在肿瘤形成过程中似乎是一个重要事件，即便不是真正的致病事件。这种在其他方面相当罕见的疾病的独特特征最近引起了强烈的研究兴趣。正如在其他类型白血病中连续细胞系是强大的研究工具一样，使用源自APL的细胞系的研究为揭示APL的病理生物学和白血病发生机制贡献了大量相关数据。据报道，有三种细胞系源自APL患者：HL-60、NB-4和PL-21。HL-60和PL-21均缺乏t(15;17)，而NB-4带有APL典型的这种细胞遗传学特征。对这些细胞系进行形态学和免疫表型检查无法明确将其归为髓单核细胞分化的任何阶段。一些额外的数据，如髓过氧化物酶、单核细胞特异性酯酶和膜联蛋白VIII的表达，连同细胞遗传学和分子生物学信息表明，NB-4是唯一真正的早幼粒细胞白血病细胞系，而HL-60可能代表晚幼粒细胞和早幼粒细胞之间的一个离散分化阶段；PL-21具有与单核细胞相关的独特特征。这些细胞系为研究正常和白血病髓单核细胞的增殖和分化所涉及的细胞和分子事件提供了独特的体外模型系统。
