Creation of a human T-ALL cell line online database

Human cell lines are used widely in biomedical research, including oncology. Lines are often chosen for study based on their cell lineage, differentiation state, and – in the case of cancer studies – because they are believed to represent key features of a particular type of malignancy. For some studies, a cell line may be chosen due to its expression of a key gene or protein, activation of a known pathway, or because it harbors a specific genetic lesion, such as a translocation or mutation in a known oncogene or tumor suppressor. With the advent of nextgeneration sequencing technologies, many cell lines have now been genomically sequenced with data also available on their gene expression profiles. T-cell acute lymphoblastic leukemia (T-ALL) is one neoplasia type for which many human cell lines exist with abundant publicly accessible data. However, despite many T-ALL cell line resources being available, many lack certain lines and/or select pieces of information. Moreover, in some cases, different sources may list contradictory data for the same cell line, either due to erroneous information, contamination by another cell line, or because cell lines may undergo genetic drift in vitro, creating new sublines with distinct features in different laboratories [1–3]. Consequently, because no single repository lists all of this data in a central location, meticulous effort is required to gather this information from multiple sources, scrutinize it, and then collate it into a meaningful format for comparing between lines. To address this deficiency, here we report the creation of a ‘Human T-ALL Cell Line database,’ accessible at the following web portal: https://humantallcelllines.wordpress. com. Table 1 displays a greatly simplified version of one page from this database. This comprehensive online compilation lists information in several categories for many widely used T-ALL lines, with hyperlinks to key publications and other online sources where this data can be explored in even greater detail. Importantly, we actively curate this database, so it represents a ‘living document’ where new information can also be deposited when it becomes available based on input from other scientists, including additional T-ALL lines or new data categories. The website provides a simple platform for users to communicate such requests or other suggestions to expand the database and improve its functionality. Key elements of Table 1 (listed in greater detail online with links to references for each item in every category) include each line’s surface phenotype with respect to CD3, CD4, CD8 (column B) and TCR (column C), known translocations (column D) with the oncogene(s) they impact, and each line’s classification according to a schema based on oncogene expression profiling and expanded to include early T-cell precursor leukemia (ETPALL), a subsequently described entity (column E) [4–6]. In addition, Table 1 lists the mutational status of key T-ALL oncogenes and tumor suppressors, including CDKN2A, NOTCH1, PTEN, TP53, and others (columns F-P). As mentioned earlier, different sources sometimes list conflicting information with regard to mutation status (e.g. for the MOLT-4 T-ALL line, TP53 was reported to have a point mutation by one group [7], whereas a second group found a novel insertion instead) [8]. In some cases, this data may be factually inaccurate. However, it is likely that many of these circumstances result from in vitro drift of the cell line, such that both mutational statuses are correct, depending upon the specific cell line isolate present in a particular laboratory. Due to this possibility, in such cases, we list both results, to make investigators aware of this ambiguity and prompt them to determine the status of the line in their possession, if it might impact their particular research application. Other elements available online not shown in Table 1 include patient demographic features pertaining to each line’s origin, notable biologic characteristics, gene and protein expression data, sensitivity to gamma-secretase inhibitors and glucocorticoids, expanded mutation information, and hyperlinks to relevant websites and publications. The database currently lists comprehensive data for 22 T-ALL lines for which we were able to retrieve extensive information: ALL-SIL, CCRF-CEM, D1.1, DND-41, DU.528, HPB-ALL, HSB-2, JURKAT, KARPAS-45, KOPT-K1, LOUCY,