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

Area of Science:

• Cell Biology
• Genetics
• Hematology

Background:

• The THP-1 cell line is a widely utilized model for acute myeloid leukemia (AML) research, particularly for MLL fusions, and for studying monocyte differentiation and function.
• Investigating THP-1 cell lines from different biorepositories is crucial due to their extensive use in scientific research.

Purpose of the Study:

• To assess the genetic consistency and reliability of THP-1 cell lines obtained from distinct biorepositories.
• To identify potential genetic drift and its impact on the utility of THP-1 cells as research models.

Main Methods:

• Comparative analysis of short tandem repeat (STR) profiles for genetic relatedness.
• Detailed examination of HLA typing, cytogenetic aberrations, and gene expression profiles, including AML-related genes.
• Identification of chromosomal regions affected by loss of heterozygosity (LOH).

Main Results:

• THP-1 cell lines exhibited high STR profile similarity (93.75%-100%) but presented discordant HLA types, cytogenetic aberrations, and AML-related gene expression.
• Loss of heterozygosity (LOH) in five chromosomal regions was identified as a primary cause of genetic discrepancies.
• Aberrant expression of key leukemia genes (LIN28B, MEIS1, SPARC) and defective HLA molecule expression were observed.

Conclusions:

• Significant genetic drift can occur in cell lines like THP-1, even with minor STR profile differences, potentially compromising research reliability.
• The observed genetic variations raise concerns about the suitability of certain THP-1 cell lines for accurate acute myeloid leukemia (AML) and antigen presentation studies.
• Researchers should be vigilant about cell line authenticity and potential genetic drift to ensure the validity of experimental findings.