False human hematopoietic cell lines: cross-contaminations and misinterpretations

Abstract

nized in the scientific community. Even if the contaminating cells have only a slight growth advantage, the intruding cells will overgrow and completely replace the original cell line, sooner or later. The most notorious culprit of such cross-contamination is, of course, the infamous solid tumor cell line HeLa. 3 The history of cell cross-contamination in cell cultures is long and painful; the first report on cell line cross-contamination appeared in 1957. [4][5][6][7][8][9] The advent of forensic DNA profiling and its application to cell line identity testing now permits the detection and identification of cell line crosscontamination with levels of sensitivity and accuracy greatly surpassing those achievable in classical surveys. The salient aspects of this common cell culture problem have been highlighted in a recent review. 9 It has been estimated that more than one-third (!) of cell cultures in use are cross-contaminated either with cells from other species (interspecies contamination) or with unrelated cells from the same species (intraspecies contamination). 9 Such cell cultures may be grown, maintained, and used for years, and results may be published without documented authenticity of the cells. The potential problems and even dangers in using cross-contaminated cell cultures for the quality of research and production in virtually any scientific or biomedical area cannot be overemphasized (invalid research results, financial loss, bodily harm, etc).Our cell line bank experience shows that in a recent series from 1990 to 1998 a large percentage of allegedly new human cell lines (cell lines derived from solid tumors and hematopoietic malignancies) which were received from the original investigators (in contrast to cell cultures obtained from secondary sources) were cross-contaminated with other cell lines: 10• 45/252 (18%) human cell lines were false; • 27/93 (29%) original donors supplied false cell lines. High incidence of cross-contaminated cell linesOur data on cross-contaminated cell lines quoted above are, presumably, only the tip of the iceberg: as pointed out, these findings refer to cell lines which were received from the original investigators. Commonly, cell lines are passed from laboratory to laboratory and here the percentages of false cell lines are definitely higher. While undoubtedly the majority of cases go unnoticed or are occasionally detected and then silently corrected, the frequency of intra-and interspecies contamination events can be surmised from several publications that offer résumés of experiences with cultures submitted specifically for monitoring and excluding crosscontamination.Nelson-Rees et al [5][6][7]11 found that 41/253 (16%) cell cultures from 45 laboratories were not as they were purported to be;

Karyotypic dissection of Hodgkin's disease cell lines reveals ectopic subtelomeres and ribosomal DNA at sites of multiple jumping translocations and genomic amplification

“…47 Of the remainder, AG-F and CO are cross-contaminated in both cases by the T cell ALL cell line, CCRF-CEM. 82 Hence, the characterization of the shortlisted HDLM-1/2/3, KM-H2, L-428 and L-540 assumes added importance. By portraying the cytogenetic picture of HD, the claim of HDLM cells to act as in vitro models is strengthened.…”

Establishment of the B cell precursor acute lymphoblastic leukemia cell line MUTZ-5 carrying a (12;13) translocation

“…1,4 Details of the various methods employed for the identity and quality control and characterization of MUTZ-5 cells have been described elsewhere: DNA fingerprinting, 5 immunophenotyping using flow cytometry and fluorescence microscopy, 6 cytokine proliferation assay, 7 immunoglobulin gene rearrangement analysis, 8 cytogenetic preparation and analysis, 9,10 viral and mycoplasmal evaluation. 6,11 The immunomarkers employed are summarized in Table 1.…”

Development and characterization of T cell leukemia cell lines established from SCL/LMO1 double transgenic mice

“…[1][2][3] Immortal cell lines provide an inexhaustible source of homogeneous, defined malignant cells free from contamination with normal blood elements. Conversely, one of the most prominent disadvantages of using malignant cell lines as a model for primary malignancy is the possibility that the cells which become immortalized were selected for their ability to grow in vitro, and that the immortalized cell lines may not be truly representative of the primary malignancy.…”

“…Conversely, one of the most prominent disadvantages of using malignant cell lines as a model for primary malignancy is the possibility that the cells which become immortalized were selected for their ability to grow in vitro, and that the immortalized cell lines may not be truly representative of the primary malignancy. [1][2][3] Two of the genes commonly activated in patients with T cell acute lymphoblastic leukemia (T-ALL) or lymphoblastic lymphoma are SCL/tal (hereafter SCL) and LMO1. 4,5 It has recently been shown that SCL and LMO1 (or the closely related LMO2) proteins collaborate to induce T cell leukemia or lymphoma in transgenic mice.…”