Major multilevel molecular divergence between THP‐1 cells from different biorepositories

• Published in: International journal of cancer Vol. 147; no. 7; pp. 2000 - 2006
• Main Authors: Noronha, Nandita, Ehx, Grégory, Meunier, Marie‐Christine, Laverdure, Jean‐Philippe, Thériault, Catherine, Perreault, Claude
• Format: Journal Article Web Resource
• Language: English
• Published: Hoboken, USA John Wiley & Sons, Inc 01.10.2020; Wiley Subscription Services, Inc; John Wiley & Sons
• Subjects: Acute myeloid leukemia; Algorithms; Antigen presentation; Biological Specimen Banks; Cancer; Cell Adhesion; Cytogenetic Analysis; Cytogenetics; DNA copy number variations; Gene expression; Gene Expression Profiling; Genetic drift; Heterozygosity; histocompatibility; Histocompatibility antigen HLA; Histocompatibility Testing; Histone-Lysine N-Methyltransferase - genetics; Human health sciences; Humans; Leukemia; Loss of Heterozygosity; Medical research; Microsatellite Repeats; Models, Biological; Monocytes; Myeloid leukemia; Myeloid-Lymphoid Leukemia Protein - genetics; Oncogene Proteins, Fusion - genetics; Oncologie; Oncology; Osteonectin; Reproducibility; Reproducibility of Results; Sciences de la santé humaine; Sequence Analysis, RNA; THP-1 Cells - cytology; THP-1 Cells - metabolism; THP‐1 cells; transcriptomics; reproducibility of results; THP-1 cells; transcriptomics; histocompatibility; acute myeloid leukemia; DNA copy number variations
• ISSN: 0020-7136; 1097-0215; 1097-0215
• DOI: 10.1002/ijc.32967

The THP‐1 cell line is broadly used as a model for acute myeloid leukemia (AML) with MLL fusion and to study monocyte differentiation and function. We studied THP‐1 cells obtained from two major biorepositories. The two cell lines were closely related with a percentage match of short tandem repeat (STR) profiles ranging from 93.75% to 100%, depending on the algorithm used. Nevertheless, we found that the two cell lines presented discordant HLA type, cytogenetic aberrations and AML‐related gene expression (including critical targets of MLL fusion). These discrepancies resulted mainly from loss of heterozygosity (LOH) involving five chromosomal regions. In view of their aberrant expression of key “leukemia” genes (e.g., LIN28B, MEIS1 and SPARC), we argue that one of the THP‐1 cell lines may not be a reliable model for studying leukemia. Their defective expression of HLA molecules and abnormal adhesion properties is also a caveat for studies of antigen presentation. In a more general perspective, our findings show that seemingly minor discrepancies in STR profiles among cell lines may be the sign of major genetic drift, of sufficient magnitude to affect the reliability of cell line‐based research. What's new? Human monocytic THP‐1 cells are widely used for the study of myeloid leukemias. It remains unclear, however, to what degree THP‐1 cell lines available from biorepositories differ. Here, THP‐1 cells obtained from two major repositories were investigated using a multi‐omics approach. The two cell lines were found to have numerous genomic, transcriptomic, and proteomic discrepancies, with pervasive effects on genes that serve critical roles in leukemogenesis. The findings indicate that the two THP‐1 cell lines differ markedly, with evidence of biologically significant genetic drift that is likely to be underestimated by analyses of short tandem repeats.