I am a hematologist involved in patient care, clinical and translation research in the field of malignant lymphoma. I focus on translational medicine on diffuse large B cell lymphoma and mantle cell lymphoma. My question by all our findings: how does the patient profit or does it help me to treat the patients. The focus of my research group is on DNA repair, cell cycle and cell death. We test novel combinations of existing anti-cancer agents to ultimately improve the treatment of patients suffering from lymphoma. I participate in the organization of new clinical trials both international (European Mantle cell Lymphoma Network) and national (HOVON). Moreover, I am actively involved in clinical trials concerning the application of CAR T cells for patient with lymphoma.
WEE1 Inhibition Enhances Anti-Apoptotic Dependency as a Result of Premature Mitotic Entry and DNA Damage
Published in: Cancers
Genomically unstable cancers are dependent on specific cell cycle checkpoints to maintain viability and prevent apoptosis. The cell cycle checkpoint protein WEE1 is highly expressed in genomically unstable cancers, including diffuse large B-cell lymphoma (DLBCL). Although WEE1 inhibition effectively induces apoptosis in cancer cells, the effect of WEE1 inhibition on anti-apoptotic dependency is not well understood. We show that inhibition of WEE1 by AZD1775 induces DNA damage and pre-mitotic entry in DLBCL, thereby enhancing dependency on BCL-2 and/or MCL-1. Combining AZD1775 with anti-apoptotic inhibitors such as venetoclax (BCL-2i)...
Tumour necrosis as assessed with F-18-FDG PET is a potential prognostic marker in diffuse large B cell lymphoma independent of MYC rearrangements
Published in: European Radiology
OBJECTIVES: MYC gene rearrangements in diffuse large B cell lymphomas (DLBCLs) result in high proliferation rates and are associated with a poor prognosis. Strong proliferation is associated with high metabolic demand and tumour necrosis. The aim of this study was to investigate differences in the presence of necrosis and semiquantitative 18F-FDG PET metrics between DLBCL cases with or without a MYC rearrangement. The prognostic impact of necrosis and semiquantitative 18F-FDG PET parameters was investigated in an explorative survival analysis. METHODS: Fluorescence in situ hybridisation analysis for MYC rearrangements,...
Xaver U Kahle, Menno Hovingh,
Walter Noordzij,
Annika Seitz,
Arjan Diepstra,
Lydia Visser,
Anke van den Berg,
Tom van Meerten,
Gerwin Huls,
Ronald Boellaard,
Thomas C Kwee,
Marcel Nijland
CD47 Expression Defines Efficacy of Rituximab with CHOP in Non-Germinal Center B-cell (Non-GCB) Diffuse Large B-cell Lymphoma Patients (DLBCL), but Not in GCB DLBCL
Published in: Cancer immunology research
Addition of rituximab (R) to “CHOP” (cyclophosphamide, doxorubicin, vincristine, and prednisone) chemotherapy improved outcome for diffuse large B-cell lymphoma (DLBCL) patients. Approximately 40% of patients who receive R-CHOP still succumb to disease due to intrinsic resistance or relapse. A potential negative regulator of DLBCL treatment outcome is the CD47 “don’t eat me” immune checkpoint. To delineate the impact of CD47, we used a clinically and molecularly well-annotated cohort of 939 DLBCL patients, comprising both germinal center B-cell (GCB) and non-GCB DLBCL subtypes, treated with either CHOP or R-CHOP....
Renee Bouwstra, Yuan He, Janneke Willemien de Boer,
Hilde Kooistra, Ewa Cendrowicz,
Rudolf S N Fehrmann,
Emanuele Ammatuna, Christine Eulenburg,
Marcel Nijland,
Gerwin Huls,
Edwin Bremer,
Tom van Meerten
Relationship between semiquantitative 18F-fluorodeoxyglucose positron emission tomography metrics and necrosis in classical Hodgkin lymphoma
Published in: Scientific Reports
Semiquantitative 18F-fluoro-2-deoxy-D-glucose positron emission tomography (18F-FDG PET) parameters have been proposed as prognostic markers in classical Hodgkin lymphoma (cHL). In non-Hodgkin lymphoma necrosis as assessed by 18F-FDG PET or computed tomography (CT) (necrosisvisual) correlates with an adverse prognosis. We investigated whether semiquantitative 18F-FDG PET metrics correlate with necrosisvisual, determined the incidence of necrosisvisual and explored the prognostic impact of these factors in cHL. From 87 cHL cases treated with ABVD, (escalated) BEACOPP or CHOP chemotherapy between 2010 and 2017, 71 had both a NEDPAS/EARL accredited 18F-FDG PET and...
Cancer cell-expressed SLAMF7 is not required for CD47-mediated phagocytosis
Published in: Nature Communications
CD47 is a prominent new target in cancer immunotherapy, with antagonistic antibodies currently being evaluated in clinical trials. For effective evaluation of this strategy it is crucial to identify which patients are suited for CD47-targeted therapy. In this respect, expression of the pro-phagocytic signal SLAMF7 on both macrophages and cancer cells was recently reported to be a requisite for CD47 antibody-mediated phagocytosis. Here, we demonstrate that in fact SLAMF7 expression on cancer cells is not required and does not impact on CD47 antibody therapy. Moreover, SLAMF7 also does...
Yuan He, Renee Bouwstra,
Valerie R. Wiersma, Mathilde de Jong,
Harm Jan Lourens,
Rudolf Fehrmann,
Marco de Bruyn,
Emanuele Ammatuna,
Gerwin Huls,
Tom van Meerten,
Edwin Bremer