Transcriptomic characterisation of acute myeloid leukemia cell lines bearing the same t(9;11) driver mutation reveals different molecular signatures

Abstract

Abstract Background 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. Results 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. Conclusion 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.

Keywords

• Leukemia
• Acute myeloid leukemia
• Comparative transcriptomics
• Zinc finger (ZNF) transcriptional repressors