Cancer and Leukaemia Epigenetics and Biology Program, Josep Carreras Leukaemia Research Institute (IJC), 08916, Badalona, Spain.
Program for Predictive and Personalized Medicine of Cancer, Germans Trias i Pujol Research Institute (PMPPC-IGTP), Campus Can Ruti, 08916, Badalona, Spain.
Sci Rep. 2021 Oct 27;11(1):21145. doi: 10.1038/s41598-021-00623-w.
Haematopoietic malignancies are frequently characterized by karyotypic abnormalities. The development of targeted drugs has been pioneered with compounds against gene products of fusion genes caused by chromosomal translocations. While polysomies are equally frequent as translocations, for many of them we are lacking therapeutic approaches aimed at synthetic lethality. Here, we report two new cell lines, named MBU-7 and MBU-8, that differ in complete trisomy of chromosome18, a partial trisomy of chromosome 7 and a tetrasomy of the p-arm of chromosome 8, but otherwise share the same mutational pattern and complex karyotype. Both cell lines are divergent clones of U-937 cells and have the morphology and immunoprofile of monocytic cells. The distinct karyotypic differences between MBU-7 and MBU-8 are associated with a difference in the specific response to nucleoside analogues. Taken together, we propose the MBU-7 and MBU-8 cell lines described here as suitable in vitro models for screening and testing vulnerabilities that are associated with the disease-relevant polysomies of chromosome 7, 8 and 18.
血液系统恶性肿瘤常表现为细胞遗传学异常。靶向药物的开发是针对染色体易位引起的融合基因的基因产物的化合物开创的。虽然多倍体与易位同样常见，但对于其中许多多倍体，我们缺乏旨在达到合成致死的治疗方法。在这里，我们报告了两个新的细胞系，分别命名为 MBU-7 和 MBU-8，它们在 18 号染色体完全三体性、7 号染色体部分三体性和 8 号染色体 p 臂的四体性方面存在差异，但在其他方面具有相同的突变模式和复杂的核型。这两个细胞系都是 U-937 细胞的不同分化克隆，具有单核细胞的形态和免疫表型。MBU-7 和 MBU-8 之间明显的核型差异与核苷类似物的特异性反应不同有关。总之，我们提出这里描述的 MBU-7 和 MBU-8 细胞系可作为体外筛选和测试与疾病相关的 7、8 和 18 号染色体多倍体相关脆弱性的合适模型。
