Georges Elise, Ho William, Iturritza Miren Urrutia, Eory Lel, Malysz Kamila, Sobhiafshar Ulduz, Archibald Alan L, Macqueen Daniel J, Shih Barbara, Garrick David, Vernimmen Douglas
The Roslin Institute and Royal (Dick) School of Veterinary Studies, University of Edinburgh, Easter Bush, Midlothian, EH25 9RG, UK.
Present Address: Division of Biomedical and Life Sciences, Faculty of Health and Medicine, Lancaster University, Lancaster, UK.
BMC Genomics. 2025 Mar 25;26(1):300. doi: 10.1186/s12864-025-11415-1.
Acute myeloid leukemia (AML) is the most common type of acute leukemia, accounting for 20% of cases in children and adolescents. Genome-wide studies have identified genes that are commonly mutated in AML, including many epigenetic regulators involved in either DNA methylation (DNMT3A, TET2, IDH1/2) or histone post-translational modifications (ASXL1, EZH2, MLL1). Several cell lines derived from AML patients are widely used in cancer research. Whether important differences in these cell lines exist remains poorly characterised.
Here, we used RNA sequencing (RNA-Seq) to contrast the transcriptome of four commonly used AML-derived cell lines: THP-1, NOMO-1, MOLM-13 bearing the common initiating t(9;11) translocation, and MV4.11 bearing the t(4;11) translocation. Gene set enrichment analyses and comparison of key transcription and epigenetic regulator genes revealed important differences in the transcriptome, distinguishing these AML models. Among these, we found striking differences in the expression of clusters of genes located on chromosome 19 encoding Zinc Finger (ZNF) transcriptional repressors. Low expression of many ZNF genes within these clusters is associated with poor survival in AML patients.
The present study offers a valuable resource by providing a detailed comparative characterisation of the transcriptome of cell lines within the same AML subtype used as models for leukemia research.
急性髓系白血病（AML）是最常见的急性白血病类型，占儿童和青少年病例的20%。全基因组研究已鉴定出在AML中常见突变的基因，包括许多参与DNA甲基化（DNMT3A、TET2、IDH1/2）或组蛋白翻译后修饰（ASXL1、EZH2、MLL1）的表观遗传调节因子。几种源自AML患者的细胞系被广泛用于癌症研究。这些细胞系中是否存在重要差异仍未得到充分表征。
在此，我们使用RNA测序（RNA-Seq）来对比四种常用的源自AML的细胞系的转录组：THP-1、NOMO-1、携带常见起始t(9;11)易位的MOLM-13以及携带t(4;11)易位的MV4.11。基因集富集分析以及关键转录和表观遗传调节因子基因的比较揭示了转录组中的重要差异，从而区分了这些AML模型。其中，我们发现位于19号染色体上编码锌指（ZNF）转录抑制因子的基因簇的表达存在显著差异。这些基因簇中许多ZNF基因的低表达与AML患者的不良生存相关。
本研究通过提供对用作白血病研究模型的同一AML亚型内细胞系转录组的详细比较特征，提供了有价值的资源。
