Department of Molecular and Clinical Cancer Medicine, University of Liverpool, Liverpool, UK.
Royal Liverpool & Broadgreen University Hospitals NHS Trust, Liverpool, UK.
Leuk Lymphoma. 2021 Jan;62(1):45-57. doi: 10.1080/10428194.2020.1811274. Epub 2020 Aug 28.
The interaction between Chronic lymphocytic leukemia (CLL) cells and monocyte-derived nurse-like cells (NLCs) is fundamentally important to CLL biology. However, studies of how CLL cells and NLCs interact have been hampered by the need for freshly obtained CLL blood samples, coupled with wide variation in the number of monocytes present in the blood of individual patients. Here, we report the development and validation of a cell-line model of NLCs which overcomes these difficulties. Co-culture of primary CLL cells with THP-1 cells induced to differentiate into macrophages by phorbol 12-myristate 13-acetate (PMA) significantly reduced both spontaneous and fludarabine-induced cell death of leukemic cells. Furthermore, compared with their M1-polarized counterparts, M2-polarized macrophages derived from PMA-differentiated THP-1 cells conferred to CLL cells greater protection from spontaneous and fludarabine-induced apoptosis. Since NLCs resemble M2 tumor-associated macrophages, this cell-line model could be useful for investigating the mechanisms through which NLCs protect CLL cells from spontaneous and drug-induced apoptosis.
慢性淋巴细胞白血病（CLL）细胞与单核细胞衍生的类护士细胞（NLC）之间的相互作用对于 CLL 生物学至关重要。然而，由于需要新鲜获得 CLL 血液样本，以及个体患者血液中单核细胞数量的广泛变化，因此对 CLL 细胞和 NLC 之间相互作用的研究受到了阻碍。在这里，我们报告了克服这些困难的 NLC 细胞系模型的开发和验证。用佛波醇 12-肉豆蔻酸 13-乙酸酯（PMA）诱导原代 CLL 细胞与 THP-1 细胞共培养，可显著降低白血病细胞的自发性和氟达拉滨诱导的细胞死亡。此外，与 M1 极化的巨噬细胞相比，源自 PMA 分化的 THP-1 细胞的 M2 极化巨噬细胞赋予 CLL 细胞对自发性和氟达拉滨诱导的细胞凋亡更强的保护作用。由于 NLC 类似于 M2 肿瘤相关巨噬细胞，因此这种细胞系模型可用于研究 NLC 保护 CLL 细胞免受自发性和药物诱导的细胞凋亡的机制。
