TY - JOUR

T1 - Transcriptomic characterisation of acute myeloid leukemia cell lines bearing the same t(9;11) driver mutation reveals different molecular signatures

AU - Georges, Elise

AU - Ho, William

AU - Iturritza, Miren Urrutia

AU - Eory, Lel

AU - Malysz, Kamila

AU - Sobhiafshar, Ulduz

AU - Archibald, Alan L.

AU - Macqueen, Daniel J.

AU - Shih, Barbara

AU - Garrick, David

AU - Vernimmen, Douglas

PY - 2025/3/25

Y1 - 2025/3/25

N2 - 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.

AB - 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.

KW - Leukemia

KW - Zinc finger (ZNF) transcriptional repressors

KW - Acute myeloid leukemia

KW - Comparative transcriptomics

U2 - 10.1186/s12864-025-11415-1

DO - 10.1186/s12864-025-11415-1

M3 - Journal article

VL - 26

JO - BMC Genomics

JF - BMC Genomics

SN - 1471-2164

IS - 1

M1 - 300

ER -