About the PhD thesis

Diffuse large B-cell lymphoma (DLBCL) is a common type of cancer arising from B-cells. Despite receiving first- or second-line treatments, many patients develop re-sistance and die. There is therefore a need for identification of genes and mecha-nisms affecting drug response within DLBCL tumor cells. The aim of this PhD is to elucidate the genetic determinants of drug response in DLBCL. This PhD project in-cludes four experimental and bioinformatical studies:

Study I characterized the mutational landscape of DLBCL to identify genes associ-ated with drug resistance to first-line treatment. This study revealed that MYD88 mutations are associated with disease progression in DLBCL.

In Study II, a bendamustine resistance gene signature, able to assign probabilities of bendamustine resistance to different subtypes of DLBCL and MM patients, was developed.

In Study III, genes associated with response to platinum-based drugs were identi-fied using genome-wide CRISPR/Cas9 screens. The study revealed that DNA dam-age response genes and BTK play essential roles in response to platinum-based drugs.

In Study IV, combination treatment with cisplatin and the Hsp90 inhibitor 17AAG was investigated. 17AAG sensitized DLBCL cells to cisplatin and resulted in in-creased levels of DNA damage and apoptosis.

The work presented in this PhD project contributes to our knowledge of drug re-sponse mechanisms in DLBCL. The genes identified from the analysis of DLBCL tumors and in vitro experiments lay the foundation for deeper investigation into their mechanistic roles in drug response and their targetability in clinical settings, aiming to improve treatment response and survival of DLBCL patients.