Matsuo Y, Drexler H G
Fujisaki Cell Center, Hayashibara Biochemical Laboratories, Okayama, Japan.
Leuk Res. 1998 Jul;22(7):567-79. doi: 10.1016/s0145-2126(98)00050-2.
A large number of continuous human leukemia cell lines have been established over the last three decades. Clearly, leukemia cell lines have become important research tools. Here, we have summarized the immunological, molecular and standard cytogenetic features of a panel of well characterized B cell precursor (BCP)-leukemia cell lines which were derived from patients with acute lymphoblastic/undifferentiated leukemia (ALL/AUL) or chronic myeloid leukemia (CML) in blast crisis. Following the recently proposed immunological EGIL classification, we assigned our panel of 27 BCP-cell lines to one of the following categories: B-I pro-B cell line; B-II common-B cell line; and B-III pre-B cell line. All cell lines express general B-lineage associated surface markers (HLA-DR, CD22, CD79a) being negative for surface immunoglobulin (Ig); the differences between the subgroups reside in expression of CD10 and cytoplasmic Ig. Several BCP-cell lines show the myelomonocytic cell-associated markers CD13 and/or CD33. These immunologically 'biphenotypic' BCP-cell lines are generally TdT+ CD10+ CD13+ CD19+ CD22+ CD34+ and carry the Philadelphia (Ph) translocation. The BCP-cell lines display surface receptors for interferon-gamma (CD119), interleukin-7 (CD127) and FLT-3 ligand (CD135). All BCP-cell lines examined have complex numerical and structural chromosomal alterations including translocations commonly seen in BCP-ALL such as t(4;11), t(9;22), t(11;19), t(12;21), and t(17;19) involving the fusion genes MLL-AF4, BCR-ABL, ENL-MLL, TEL/ETV6-AML1 and E2A-HLF, respectively. Besides the expected rearrangement of the Ig heavy chain receptor gene, several cell lines also have rearrangements of the T cell receptor genes beta, gamma or delta. While some BCP-cell lines express (aberrantly) myeloperoxidase at the mRNA level, most lines are negative in the immunological or cytochemical staining. Several large series documented the difficulty in establishing such BCP cell lines with success rates in the range of 10-20% (on average 15%). Still, since the establishment of the first bonafide BCP-cell line in 1974 (cell line REH), some 150 cell lines have been established of which, however, only a small percentage have been sufficiently well characterized and described. A higher success rate for immortalizing any given leukemia cell might depend on a closer emulation of the physiological in vivo microenvironment. The possibility to grow in vitro leukemia cells at will would represent ideal experimental systems permitting basic research and patient-specific investigations. In summary, the use of well-characterized BCP-cell lines provide unprecedented opportunities for studying a multitude of biological aspects related to normal and neoplastic B-lymphocytes.
在过去三十年里，已经建立了大量连续传代的人白血病细胞系。显然，白血病细胞系已成为重要的研究工具。在此，我们总结了一组特征明确的B细胞前体（BCP）白血病细胞系的免疫学、分子和标准细胞遗传学特征，这些细胞系源自急性淋巴细胞性/未分化白血病（ALL/AUL）患者或慢性粒细胞白血病（CML）急变期患者。按照最近提出的EGIL免疫学分类，我们将我们的27个BCP细胞系分为以下类别之一：B-I前B细胞系；B-II普通B细胞系；以及B-III前B细胞系。所有细胞系均表达一般的B系相关表面标志物（HLA-DR、CD22、CD79a），表面免疫球蛋白（Ig）为阴性；亚组之间的差异在于CD10和细胞质Ig的表达。几个BCP细胞系显示出与髓单核细胞相关的标志物CD13和/或CD33。这些免疫表型“双表型”的BCP细胞系通常为TdT+ CD10+ CD13+ CD19+ CD22+ CD34+，并携带费城（Ph）易位。BCP细胞系显示出干扰素-γ（CD119）、白细胞介素-7（CD127）和FLT-3配体（CD135）的表面受体。所有检测的BCP细胞系都有复杂的数量和结构染色体改变，包括BCP-ALL中常见的易位，如t(4;11)、t(9;22)、t(11;19)、t(12;21)和t(17;19)，分别涉及融合基因MLL-AF4、BCR-ABL、ENL-MLL、TEL/ETV6-AML1和E2A-HLF。除了预期的Ig重链受体基因重排外，几个细胞系还存在T细胞受体基因β、γ或δ的重排。虽然一些BCP细胞系在mRNA水平异常表达髓过氧化物酶，但大多数细胞系在免疫或细胞化学染色中为阴性。几个大系列研究记录了成功建立此类BCP细胞系的困难，成功率在10%-20%之间（平均15%）。尽管如此，自1974年第一个真正的BCP细胞系（REH细胞系）建立以来，已经建立了约150个细胞系，然而，其中只有一小部分得到了充分的特征描述。使任何给定白血病细胞永生化的更高成功率可能取决于更接近模拟体内生理微环境。随意在体外培养白血病细胞的可能性将代表理想的实验系统，可用于基础研究和针对患者的研究。总之，使用特征明确的BCP细胞系为研究与正常和肿瘤性B淋巴细胞相关的众多生物学方面提供了前所未有的机会。
