- van Keimpema M, Grüneberg LJ, Mokry M, van Boxtel R, van Zelm MC, Coffer P, Pals ST, Spaargaren M, The forkhead transcription factor FOXP1 represses human plasma cell differentiation. BLOOD 2015;126 (18):2098-2109 [PubMed]
- de Rooij MFM, Kuil A, Kater AP, Kersten MJ, Pals ST, Spaargaren M, 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 M, Grüneberg LJ, Mokry M, van Boxtel R, Koster J, Coffer PJ, Pals ST, Spaargaren M, 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 HM, Schilder-Tol EJM, Oud MECM, Noorduyn LA, Kluin PM, Kersten MJ , Spaargaren M, Pals ST, 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 MFM, Kuil A, Geest CR, Eldering E, Chang BY, Buggy JJ, Pals ST, Spaargaren M, 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]
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.
This research group participates in the Lymphoma and Myeloma Center Amsterdam (LYMMCARE) and the Cancer Center Amsterdam (CCA)
Dr. M. Spaargaren PhD
Dr. A.M. de Bruin PhD
N. Swier MSc
S.P.J. Joosten MSc
Ing. L.J. Grüneberg
Ing. A.J. Kuil
- Dean and member of the executive directory, Oncology Graduate School (OOA: Onderzoekschool Oncologie Amsterdam)
- Board of directors / Trustees / Supervisory board, Society on Tumor Cell Biology of the Dutch Cancer Society (KWF-werkgemeenschap Tumorcel biologie)
- Board of Directors (and co-founder), Lymphoma and Myeloma Center Amsterdam (LYMMCARE)
- Committee member, AMC supportgroup for grant applications of the Dutch Cancer Society (KWF kankerbestrijding)
- Member of evaluation/assessment committee for TOP and ECHO grant applications, Netherlands Organisation for Scientific Research (NWO) - division Chemical Sciences - focus area Biological/Medical sciences
- International Waldenstrom's Macroglobulinemia Foundation
- KWF Kankerbestrijding
- Stichting AMC Foundation (Vrijgesteld)