Related Experiment Video
Updated: Sep 28, 2025
Creation and Maintenance of a Living Biobank - How We Do It
Published on: April 10, 2021
THP-1 reference data: Proposal of an in vitro branched evolution model for cancer cell lines
Fumio Kasai1,2, Noriko Hirayama2, Makoto Fukushima1
1RIKEN Cell Bank, Cell Engineering Division, BioResource Research Center, Tsukuba, Japan.
Insights
Four THP-1 leukemia cell line sublines show significant genomic and transcriptomic differences due to genetic drift. RCB3686 is closest to the original THP-1, making it an optimal model for AML-M5 research.
Area of Science:
- Cell Biology
- Genomics
- Cancer Research
Background:
- THP-1 is a widely used leukemia cell line, registered under multiple accession numbers.
- Previous studies have not clarified the genetic differences between these THP-1 sublines.
- Understanding these variations is crucial for reproducible leukemia research.
Purpose of the Study:
- To comprehensively compare four distinct THP-1 cell line sublines at chromosomal and DNA sequence levels.
- To identify the subline closest to the original THP-1 for AML-M5 modeling.
- To provide a reference for classifying THP-1 progenies.
Main Methods:
- Chromosome analysis to determine ploidy.
- Target sequencing to analyze variant frequencies.
- SNP microarrays to assess genetic profiles and loss of heterozygosity.
- Short tandem repeat (STR) genotyping for subtle genetic distinctions.
- Transcriptome analysis to compare gene expression patterns.
Main Results:
- Significant differences in ploidy were observed: JCRB0112 (triploid) and RCB1189 (tetraploid).
- SNP microarrays revealed four distinct profiles with large-scale loss of heterozygosity.
- Transcriptome analysis indicated JCRB0112.1 diverged significantly from the other three lines.
- RCB3686 was identified as the most genetically similar to the original THP-1.
- All four sublines exhibited unique variant frequency patterns and STR genotypes.
Conclusions:
- The four THP-1 sublines represent independent lineages with substantial genomic and transcriptomic divergence.
- Genetic drift significantly influences gene expression in cell line subcultures.
- RCB3686 is recommended as an optimal model for Acute Myeloid Leukemia subtype M5 (AML-M5).
- STR marker comparison is proposed as a reliable method to distinguish THP-1 sublines.
Abstract:
THP-1 is a representative leukemia cell line and is registered with four different numbers in JCRB and RIKEN BRC cell banks. However, differences between these four lines remain unclear. In our study, these four THP-1 cell lines, JCRB0112, JCRB0112.1 (corresponding to ATCC TIB-202), RCB1189 (DSMZ ACC-16) and RCB3686, have been compared at chromosome and DNA sequence levels. Our results reveal that ploidy has been changed in JCRB0112 and RCB1189, which are triploid and tetraploid, respectively. Patterns of variant frequencies from target sequencing are unique to each ploidy, estimating whole genomic status based on partial sequence data. SNP microarrays showed four distinct profiles with a large-scale loss of heterozygosity, reflected in subtle differences in STR genotypes. Transcriptome patterns suggest that JCRB0112.1 has diverged highly from the other three lines. RCB1189 and JCRB0112.1 responded to PMA faster than RCB3686 and JCRB0112. We have identified RCB3686 as the closest to the original THP-1, which can be an optimal model of AML-M5. These four THP-1 genomes and transcriptomes exhibit significant differences, indicating four independent sublines and demonstrating the influence of genetic drift on gene expression. As these cells share the same name, THP-1 must be accompanied by their registration number of each cell repository. Our data provide genomic features of four THP-1 sublines and serve as a reference profile to classify widely spread THP-1 progenies, which could be distinguished by a comparison of 24 STR markers. Multiple sublines can be generated by separate cell cultures, which would be explained by in vitro branched evolution.
Related Concept Videos
02:07Tumor Progression
Colon cancer is one of the best-documented examples of tumor progression. Early mutation in the APC gene in colon cells causes a small growth on the colon wall called a polyp. With time, this polyp grows into a benign, pre-cancerous tumor. Further...
01:16Cell Lines
02:21Cancers Originate from Somatic Mutations in a Single Cell
02:53Adaptive Mechanisms in Cancer Cells
Some of the advantages that cancer cells have on normal cells include - enhanced ability to divide without terminally differentiating, induce new blood vessel formation,...