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.

中文翻译：

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来自不同生物存储库的THP-1细胞之间的主要多级分子差异。

THP-1细胞系广泛用作具有MLL融合的急性髓细胞白血病（AML）的模型，并用于研究单核细胞的分化和功能。我们研究了从两个主要生物库中获得的THP-1细胞。取决于所使用的算法，两种细胞系与短串联重复序列（STR）分布的百分比匹配密切相关，范围从93.75％到100％。然而，我们发现这两种细胞系表现出不一致的HLA类型，细胞遗传畸变和AML相关基因表达（包括MLL融合的关键靶标）。这些差异主要是由于涉及五个染色体区域的杂合性（LOH）的丧失。考虑到关键的“白血病”基因（例如LIN28B，MEIS1和SPARC），我们认为THP-1细胞系之一可能不是研究白血病的可靠模型。它们的HLA分子表达缺陷和异常的粘附特性也是研究抗原呈递的警告。从更普遍的角度来看，我们的发现表明，细胞系中STR谱中看似微小的差异可能是主要遗传漂移的迹象，其程度足以影响基于细胞系的研究的可靠性。