Abstract 1674: Correlation of the mutational pattern and gene expression data of patient-derived Non-Hodgkin lymphoma xenografts (PDX) with the response to targeted therapies

Abstract

Abstract Non-Hodgkin lymphomas (NHL) are lymphoid malignant neoplasms that represent a very heterogeneous group and still pose an important clinical challenge. In particular, the frequent development of resistance to the treatment with standard-of-care (SoC) drugs is associated with a high incidence of disease recurrence. Recent progress in molecular high-throughput profiling has helped to identify genetic drivers for many subtypes of B-cell lymphomas as well as T-cell lymphomas. Target validation and drug development depend on corresponding preclinical models representing the different subtypes. Therefore, we established and characterized a panel of patient-derived NHL xenografts. All lymphoma PDX were derived from peripheral blood, lymph node extirpations or core needle biopsies, respectively, and were routinely implanted subcutaneously into immunodeficient mice. For further characterization, established lymphoma PDX models were treated with SoC (e.g., cyclophosphamide, doxorubicine, vincristine, etoposide) and investigational drugs. To gain a deeper insight into the molecular biology of the lymphoma models, RNA sequencing was performed. More than 20 PDX models from different NHL entities have been successfully established and characterized. We observed heterogeneous individual responses to the SoC treatments as well as to target treatments such as rituximab or ibrutinib. Explorative analysis of RNA sequencing data confirmed the representation of the clinical lymphoma subgroups (e.g. DLBCL, Burkitt, AITL) in our panel of lymphoma models. Based on the RNA sequencing data, the individual Human Leukocyte Antigen (HLA) type of each lymphoma PDX was determined with the aim to enable personalized, HLA type-specific studies. Our lymphoma PDX portfolio provides an exceptional platform for the identification and validation of new targets and allows the preclinical screening of new combinations in translational research projects. Citation Format: Bernadette Brzezicha, Theresia Conrad, Michael Becker, Aitomi Bittner, Martin Janz, Clemens A. Schmitt, Ulrich Keilholz, Jens Hoffmann. Correlation of the mutational pattern and gene expression data of patient-derived Non-Hodgkin lymphoma xenografts (PDX) with the response to targeted therapies [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 1674.