Prognostic Markers and Mechanisms of Chemotherapy Resistance in Diffuse Large B-cell Lymphoma

Karin Fjordén

Research output: ThesisDoctoral Thesis (compilation)

492 Downloads (Pure)

Abstract

Diffuse large B-cell lymphoma (DLBCL) is an aggressive and heterogeneous disease. Identification of prognostic and predictive markers is important to design individualised and effective treatment strategies. This thesis describes different approaches to search for molecular prognostic markers and an attempt to overcome chemotherapy resistance in DLBCL.

In the first study it was investigated whether immunohistochemical expression of CD40, previously associated with a favourable prognosis in DLBCL, had any prognostic impact after the addition of rituximab to anthracycline-based chemotherapy. Results showed better prognosis in CD40-positive patients receiving this combined treatment. An inflammatory stromal process was observed in CD40-expressing tumours when using gene expression profiling, possibly contributing to a better prognosis in CD40-positive patients.

A study about the effect of inhibited protein prenylation on the response to CHOP therapy, using an in vitro cell-line-based model, showed that treatment with geranylgeranylation inhibitors in DLBCL cell lines had a chemo-sensitising effect. This indicates that inhibition of geranylgeranylation may prove a useful strategy for overcoming CHOP resistance in DLBCL.

A recombinant antibody microarray was used to search for prognostic protein profiles in plasma from DLBCL patients in an attempt to identify new candidate markers for the prognosis and treatment response in DLBCL and to provide a basis for future investigations and validation.

The results of this work indicated that the tumour microenvironment and host immune response contribute to the prognosis in DLBCL, and suggest a potential novel strategy to overcome chemotherapy resistance. Further molecular profiling is important for improved treatment of patients with DLBCL.
Original languageEnglish
QualificationDoctor
Awarding Institution
  • Tumor microenvironment
Supervisors/Advisors
  • Jerkeman, Mats, Supervisor
  • Drott, Kristina, Supervisor
  • Linderoth, Johan, Supervisor
  • Wingren, Christer, Supervisor
  • Borrebaeck, Carl, Supervisor
Award date2015 Mar 13
Publisher
ISBN (Print)978-91-7619-096-8
Publication statusPublished - 2015

Bibliographical note

Defence details

Date: 2015-03-13
Time: 09:00
Place: Lecture Hall in the Radiotherapy building, floor 3, Department of Oncology, Skåne University Hospital, Lund

External reviewer(s)

Name: Davies, Andrew
Title: [unknown]
Affiliation: Cancer Sciences Division, Somers Cancer Research Building, Southampton General Hospital, Southampton, UK

---

Subject classification (UKÄ)

  • Cancer and Oncology

Fingerprint

Dive into the research topics of 'Prognostic Markers and Mechanisms of Chemotherapy Resistance in Diffuse Large B-cell Lymphoma'. Together they form a unique fingerprint.

Cite this