ESTABLISHED CELL LINES AND PATIENT-DERIVED XENOGRAFTS REPRESENT EQUALLY RELEVANT MODELS OF AGGRESSIVE LYMPHOMAS

Patient-derived xenografts (PDXs) became standard tools of preclinical research bridging the gap between established cell lines and primary tumor samples. While PDXs are now generally regarded as true representatives of the particular malignancies in human, biological relevance of the cell lines has been repeatedly questioned. In this study, we robustly characterized 7 newly derived PDXs and 5 cell lines established from patients with relapsed/refractory non-Hodgkin lymphomas. In 3 cases, a PDX and a cell line were derived from one patient, which enabled their direct comparison by whole-exome sequencing (WES), locus-specific and multi-color FISH, flow cytometry, and gene expression profiling. Both the PDXs and the cell lines captured majority of somatic mutations and karyotype aberrations harbored by the original lymphoma cells with no fundamental difference between the two types of preclinical models. The FISH and WES data strongly suggest that both the cell lines and PDXs represent only subclonal populations contained within the primary lymphoma specimen. The results indicate that lymphoma cell lines represent relevant models of a small fraction of relapsed, usually treatment-refractory, microenvironment-independent, aggressive lymphomas with comlex karyotype changes enriched in aberrations of TP53, MYC and CDKN2A genes. The key difference between PDXs and cell lines appears to dwell in the capability of PDXs to be derived from less-aggressive lymphomas including microenvironment-dependent and treatment-naïve cases. Keywords: gene expression profile (GEP); mouse models; non-Hodgkin lymphoma (NHL).