Investigations on the role of translation initiation factors in aggressive B-cell lymphoma

Abstract

Diffuse large B-cell lymphoma (DLBCL) is an aggressive neoplasm affecting the lymphatic system. Although contemporary chemo-immunotherapy can cure a considerable fraction of DLBCL-patients, 40% still succumb to their disease. Importantly, one reason for this lies in the big heterogeneity of the malignancy, which is reflected, amongst others, by two disease-relevant subtypes. In order to help patients affected by this heterogeneous disease, there is thus a constant need for new diagnostic or prognostic markers, to be able to stratify patients risk a priori and to enable moreover new targeted therapies. Cellular protein synthesis begins with the translation initiation phase, a key control step of the whole process. The task of translation initiation, which is realized by so-called eukaryotic initiation factors (eIFs), is to assemble an elongation-competent ribosome on the protein-coding mRNA. Importantly, despite this crucial role in regular cell metabolism, eIFs have also been described to contribute to diverse neoplastic settings. Nevertheless, apart from specific eIFs having already been implicated in DLBCL pathogenesis, most eIFs have never been investigated in this malignancy. To fill this gap and to look for new markers for DLBCL pathogenesis, in this study, 16 eIFs were investigated for their potential disease-relevant role in DLBCL. For this aim, a cohort of primary (n=34) and secondary (n=22) DLBCL patient samples was analyzed for the mRNA expression levels of the investigated eIF-panel. As non-neoplastic controls, germinal center B-cell specimens, isolated from non-neoplastic tonsils (n=5), were used. Interestingly, 12 out of 16 eIFs were higher expressed in DLBCL than in non-neoplastic B-cell controls (p

Date of Award	2019
Original language	English
Awarding Institution	Medical University Graz
Supervisor	Johannes Haybäck (Supervisor), Rudolf Schicho (Supervisor) & Heinz Sill (Supervisor)