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PhD M. Spaargaren

Position
Associate Professor
Main activities
Education, Research
Specialisation
Oncology, Immunolgy
Focus of research

Pathogenesis of B-cell malignancies, in particular Non-Hodgkin Lymphoma (NHL), Chronic Lymphocytic Leukemia (CLL), Multiple Myeloma (MM) and Waldenström’s Macroglobulinemia (WM).


Specific interests:
- signal transduction
- cell proliferation and survival
- cell adhesion and migration
- tumor microenvironment-dependence

Favorite molecules:
- B-cell antigen receptor
- chemokines (e.g., CXCL12)
- HGF and MET
- WNT and beta-catenin
- heparan sulfate proteoglycans (e.g., Syndecan-1 and CD44)
- adhesion molecules (integrins and cadherins)
- GTPases (e.g., Ras and Ral)
- kinases (e.g., Bruton’s tyrosine kinase)
- kinase inhibitors (e.g., ibrutinib and idelalisib)
- transcription factors (e.g., FOXP1)

 

Key publications
  • van Keimpema Martine, Grüneberg Leonie J., Mokry Michal, van Boxtel Ruben, van Zelm Menno C., Coffer Paul, Pals Steven T., Spaargaren Marcel The forkhead transcription factor FOXP1 represses human plasma cell differentiation Blood 2015;126 (18):2098-2109 [PubMed]
  • de Rooij Martin F. M., Kuil Annemieke, Kater Arnon P., Kersten Marie José, Pals Steven T., Spaargaren Marcel Ibrutinib and idelalisib synergistically target BCR-controlled adhesion in MCL and CLL: a rationale for combination therapy Blood 2015;125 (14):2306-2309 [PubMed]
  • van Keimpema Martine, Grüneberg Leonie J., Mokry Michal, van Boxtel Ruben, Koster Jan, Coffer Paul J., Pals Steven T., Spaargaren Marcel FOXP1 directly represses transcription of proapoptotic genes and cooperates with NF-κB to promote survival of human B cells Blood 2014;124 (23):3431-3440 [PubMed]
  • Kraan W., van Keimpema M., Horlings H. M., Schilder-Tol E. J. M., Oud M. E. C. M., Noorduyn L. A., Kluin P. M., Kersten M. J., Spaargaren M., Pals S. T. High prevalence of oncogenic MYD88 and CD79B mutations in primary testicular diffuse large B-cell lymphoma Leukemia 2014;28 (3):719-720 [PubMed]
  • de Rooij Martin F. M., Kuil Annemieke, Geest Christian R., Eldering Eric, Chang Betty Y., Buggy Joseph J., Pals Steven T., Spaargaren Marcel The clinically active BTK inhibitor PCI-32765 targets B-cell receptor- and chemokine-controlled adhesion and migration in chronic lymphocytic leukemia Blood 2012;119 (11):2590-2594 [PubMed]
All Publications
Research programmes

PhD M. Spaargaren (Molecular pathogenesis and targeted therapy of B-cell malignancies)

Our research group (Dept. of Pathology, section Immuno- and Hematopathology) has a long-standing interest in the molecular and cellular aspects of normal B cell differentiation and function, and in the pathogenesis of B-cell malignancies, in particular Non-Hodgkin Lymphoma (NHL), Chronic Lymphocytic Leukemia (CLL) and Multiple Myeloma (MM).

As a PI in the AMC I participate in the Lymphoma and Myeloma Center Amsterdam (LYMMCARE) and in the Cancer Center Amsterdam (CCA).

The major aims of my research are:
1) identify and molecularly dissect the signaling pathways involved in differentiation and function of B cells and in the pathogenesis of B-cell malignancies;
2) explore and exploit microenvironment-dependence as the Achilles’ heel of B-cell malignancies

More specifically, regarding these aims, we explore(d) the molecular and functional aspects of signalling by the B-cell antigen receptor, chemokines (e.g. CXCL12/CXCR4), receptor tyrosine kinases (e.g., HGF/MET), and WNTs, and the role of heparan sulfate proteoglycans, adhesion molecules (integrins and cadherins), GTPases (e.g.,  Ras and Ral), kinases (e.g., Bruton’s tyrosine kinase (BTK) and PI3K), and the transcription factor FOXP1.

One of my long-standing research interests involves the molecular and functional aspects of B-cell receptor-controlled integrin-mediated adhesion and chemokine-controlled adhesion and migration of normal and malignant B cells. Our recent studies on the molecular mechanism underlying the unprecedented clinical efficacy of the recently FDA-approved Bruton’s tyrosine kinase (BTK) inhibitor Ibrutinib and phospatidylinositol-3 kinase δ (PI3K δ) inhibitor Idelalisib have established lymphoid organ retention, homing and microenvironment-dependence as a prominent therapeutic target for treatment of B-cell malignancies.

The focus of our current research will be on target- and drug-discovery and (pre-clinical) development of targeted (combination-) therapy for mantle cell lymphoma, chronic lymphocytic leukemia, diffuse large B-cell lymphoma, multiple myeloma and Waldenström Macroglobulinaemia.

Themes: Oncology

This research group participates in the Lymphoma and Myeloma Center Amsterdam (LYMMCARE) and  the Cancer Center Amsterdam (CCA)

Postdocs
M.F.M. de Rooij
R. Yuan

PhD Students
MSc S.P.J. Joosten

Others
BEng L.J. Gruneberg
BEng A. Kuil
E.J.M. Schilder-Tol
M.E.C.M. Ursem-Oud

Current research funding
  • AMC
  • KWF Kankerbestrijding
  • Stichting AMC Foundation (Vrijgesteld)