Inhibition of cell death in the pathogenesis of lymphomas 
Inhibition of cell death including apoptosis is a crucial step early in the pathogenesis of lymphomas because a) dividing non-neoplastic lymphocytes have a limited lifetime and die via apoptosis and b) neoplastic cells accumulate genetic aberrations including oncogene activations that in normal cells result in stress-induced apoptosis. 
Inhibition of cell death is not only important in the development of lymphomas but is also a major factor causing intrinsic resistance of tumor cells to chemotherapy in chemotherapy-refractory patients. Identifying the cell death inhibiting mechanisms in these lymphomas may allow the development of specific strategies that neutralize these mechanisms and tailoring therapy.  Our research is focused on

  1. identification of defects in cell death pathways in Non-Hodgkin lymphomas
  2. understanding of the mechanisms causing resistance to cell death and investigation whether these cell death inhibiting mechanisms are related to a poor clinical response to chemotherapy
  3. determination of optimal strategies to kill lymphoma cells by targeting specific apoptosis inhibiting molecules or by triggering alternative pathways of cell death
  4. predefinition of patients that will benefit of a specific therapy
  5. predefinition of lymphomas or precursor cells which will transform to a (more aggressive) lymphoma

Diffuse large B-cell lymphoma (DLBCL) 

DLBCL is the most frequent type of non-Hodgkin Lymphoma in adults. Treatment has been based on R-CHOP for years resulting in a 5-year survival of 30-80% and 50% long-term survival. From a biological point of view, DLBCL is a heterogeneous group of diseases in which several different oncogenetic pathways play a role. Information on genetic and epigenetic alterations may be used for refined classification, but increasingly so as potential tools for treatment stratification. Gene expression profiling (GEP) studies have revealed a major dichotomy in germinal center B-cell like (GCB) and activated B-cell like (ABC). Both classes are characterized by various molecular alterations that are enriched, but not unique to these classes. Moreover, next-generation sequencing results revealed also classes of alterations that are relatively independent on the GCB/ABC dichotomy. The availability of newly developed compounds brings targeted treatment based on the specific driving alterations in DLBCL within reach. It is the aim to launch a clinical trial with a Bayesian randomized design for targeted treatment in DLBCL by HOVON within 3 years.

Follicular lymphoma (FL) 

FL is the prototypical indolent B-cell lymphoma and thereby a model for a larger group of lymphoid diseases. Little is known about the early phases of oncogenesis in FL and early interactions between B-cells and their immune microenvironment
We focus our research on 

  • the development of a molecular diagnostic tool for differential diagnosis of DLBCL and BL
  • the development of tools for targeted treatment in DLBCL
  • understanding of the oncogenesis of subtypes of DLBCL


Saskia Cillessen PhD - staff member
Daphne de Jong MD PhD - staff member
Chris Meijer MD PhD - staff member
Matthias Mendeville - PhD student
L. de Baaij - PhD student
M. Radersma - PhD student
J. van de Water - PhD student