As autochthonous malignancies of the adaptive immune system, B-cell lymphomas are dependent on B-cell receptor expression and signalling. My laboratory investigates distinct mechanisms that activate B-cell receptor signalling in various lymphoma types, including autoantigenic stimulation, antigen-independent autonomous signalling, acquisition of N-glycosylation, and oncogenic mutations within the signalling cascade. In addition, the role of the lymphoma microenvironment with focus on specific, activating or inhibiting T-B cell interactions is investigated. Insight into the commonalities or differences between autoimmunity and B-cell malignancies will inspire novel approaches to inhibit essential stimulating signals and to activate immunosurveillance of pathogenic B-cell clones in autoimmunity and lymphoma.
Department of Hematology, Leiden University Medical Center, Leiden, The Netherlands
Koning MT, Kielbasa SM, Boersma V, Buermans HPJ, van der Zeeuw SAJ, van Bergen CAM, Cleven AHG, Kluin PM, Griffioen M, Navarrete MA, et al. ARTISAN PCR: rapid identification of full-length immunoglobulin rearrangements without primer binding bias. Br J Haematol. 2017.
Scherer F, van der Burgt M, Kielbasa SM, Bertinetti-Lapatki C, Duhren von Minden M, Mikesch K, Zirlik K, de Wreede L, Veelken H, Navarrete MA. Selection patterns of B-cell receptors and the natural history of follicular lymphoma. Br J Haematol. 2016.
Schneider D, Duhren-von Minden M, Alkhatib A, Setz C, van Bergen CA, Benkisser-Petersen M, Wilhelm I, Villringer S, Krysov S, Packham G, et al. Lectins from opportunistic bacteria interact with acquired variable-region glycans of surface immunoglobulin in follicular lymphoma. Blood. 2015.
Papaioannou D, Strothmeyer AM, Duhren-von Minden M, Keppler-Hafkemeyer A, Zirlik K, Mikesch K, van Bergen CA, Navarrete MA, Veelken H. Evidence for idiotype-directed immunosurveillance is restricted to follicular lymphoma and attributable to somatic hypermutation. Haematologica. 2015.
Duhren-von Minden M, Ubelhart R, Schneider D, Wossning T, Bach MP, Buchner M, Hofmann D, Surova E, Follo M, Kohler F, et al. Chronic lymphocytic leukaemia is driven by antigen-independent cell-autonomous signalling. Nature. 2012.
Florian Scherer: The role of AID in the immunobiology and pathophysiology of follicular lymphoma. Awarded: 2013
Current PhD projects
Marvyn T. Koning: Analysis of the B-cell repertoire by massive parallel sequences of complete immunoglobulin heavy and light chain transcripts in health and disease.
Janneke A. Eken: Oncogenic BCR signalling in aggressive B-cell lymphomas.
Julieta H. Sepulveda Yanez: Oncogenic AID induced mutagenesis in B-cell lymphoma.
Sebastiaan F. Somers: Unravelling genetic mutational profiles of patients with diffuse large B-cell lymphomas for the improvement of precision medicine.