Characterization of a New Chronic Lymphocytic Leukemia Cell Line for Mechanistic In Vitro and In Vivo Studies Relevant to Disease

Studies of chronic lymphocytic leukemia (CLL) have yielded substantial progress, however a lack of immortalized cell lines representative of the primary disease has hampered a full understanding of disease pathogenesis and development of new treatments. Here we describe a novel CLL cell line (OSU-CLL) generated by EBV transformation, which displays a similar cytogenetic and immunophenotype observed in the patient’s CLL (CD5 positive with trisomy 12 and 19). A companion cell line was also generated from the same patient (OSU-NB). This cell line lacked typical CLL characteristics, and is likely derived from the patient’s normal B cells. In vitro migration assays demonstrated that OSU-CLL exhibits migratory properties similar to primary CLL cells whereas OSU-NB has significantly reduced ability to migrate spontaneously or towards chemokine. Microarray analysis demonstrated distinct gene expression patterns in the two cell lines, including genes on chromosomes 12 and 19, which is consistent with the cytogenetic profile in this cell line. Finally, OSU-CLL was readily transplantable into NOG mice, producing uniform engraftment by three weeks with leukemic cells detectable in the peripheral blood spleen and bone marrow. These studies describe a new CLL cell line that extends currently available models to study gene function in this disease.慢性淋巴细胞白血病（chronic lymphocytic leukemia, CLL）领域的研究已取得显著进展，但由于缺乏可代表原发疾病的永生化细胞系，阻碍了学界对其发病机制的全面解析以及新型治疗手段的开发。本研究报道了一种通过爱泼斯坦-巴尔病毒（Epstein-Barr virus, EBV）转化构建的新型CLL细胞系（OSU-CLL），其细胞遗传学特征与免疫表型均与患者体内的CLL细胞一致：CD5阳性，且携带12号与19号染色体三体。研究人员同时从同一患者体内构建了配套细胞系（OSU-NB），该细胞系不具备典型的CLL特征，推测其起源于患者体内的正常B淋巴细胞。体外迁移实验结果显示，OSU-CLL的迁移特性与原发CLL细胞相似，而OSU-NB的自发迁移及向趋化因子迁移的能力均显著降低。基因芯片（microarray）分析显示，两种细胞系的基因表达谱存在显著差异，其中包括12号与19号染色体上的基因，这与该细胞系的细胞遗传学特征谱相符。最后，OSU-CLL可稳定移植至NOG小鼠体内，三周后即可实现均匀植入，且在外周血、脾脏与骨髓中均可检测到白血病细胞。本研究构建的新型CLL细胞系，拓展了当前用于研究该疾病基因功能的现有疾病模型体系。