- Bende Richard J., Aarts Wilhelmina M., Riedl Robert G., de Jong Daphne, Pals Steven T., van Noesel Carel J. M. Among B cell non-Hodgkin's lymphomas, MALT lymphomas express a unique antibody repertoire with frequent rheumatoid factor reactivity Journal of experimental medicine 2005;201 (8):1229-1241 [PubMed]
- Bende Richard J., van Maldegem Febe, Triesscheijn Martijn, Wormhoudt Thera A. M., Guijt Richard, van Noesel Carel J. M. Germinal centers in human lymph nodes contain reactivated memory B cells Journal of experimental medicine 2007;204 (11):2655-2665 [PubMed]
- Hoogeboom Robbert, van Kessel Kok P. M., Hochstenbach Frans, Wormhoudt Thera A., Reinten Roy J. A., Wagner Koen, Kater Arnon P., Guikema Jeroen E. J., Bende Richard J., van Noesel Carel J. M. A mutated B cell chronic lymphocytic leukemia subset that recognizes and responds to fungi Journal of experimental medicine 2013;210 (1):59-70 [PubMed]
- Boparai Karam S., Dekker Evelien, van Eeden Susanne, Polak Mirjam M., Bartelsman Joep F. W. M., Mathus-Vliegen Elisbeth M. H., Keller Josbert J., van Noesel Carel J. M. Hyperplastic polyps and sessile serrated adenomas as a phenotypic expression of MYH-associated polyposis Gastroenterology 2008;135 (6):2014-2018 [PubMed]
- Boparai Karam S., Dekker Evelien, Polak Mirjam M., Musler Alex R., van Eeden Susanne, van Noesel Carel J. M. A Serrated Colorectal Cancer Pathway Predominates over the Classic WNT Pathway in Patients with Hyperplastic Polyposis Syndrome American journal of pathology 2011;178 (6):2700-2707 [PubMed]
Prof. PhD C.J.M. van Noesel (B cell biology and the pathogenesis of B-NHL/ The serrated neoplasia pathway to colorectal cancer)
Dr. Carel van Noesel, is a clinical pathologist engaged in the diagnostics of hemato-, gastrointestinal and molecular pathology. He is head of the Molecular Diagnostics unit at his department and has a chair in ‘Molecular Pathology’. The research of his group focussus on (I) the pathogenesis of malignant B-cell lymphomas, and (II) more recently on the serrated neoplasia pathway to colonic cancer.
Ad (I): Ample evidence exists that B cell lymphomagenesis in man etiologically relates to germinal center (GC) transit. During this accelerated differentiation phase,proliferating B cells are genetically unstable as they modify their immunoglobulin variable (IgV) and switch region genes and to a lesser extent also non-immunoglobulin genes. As a consequence, B-NHL are in majority of (post-) GC phenotype and harbor chromosomal translocations involving the immunoglobulin genes.
As yet, it was assumed that B-cell transformation occurs during a single, unfortunate GC reaction. We recently provided evidence that memory B cells can repeatedly engage in GC reactions in human lymph nodes. We therefore envision an alternative mechanism of B cell lymphomagenesis in which the transforming events do not necessarily occur during a single GC passage but, in parallel to the gain of IgV mutations, gradually accumulate in memory B cells during successive recall responses throughout life. This scenario explains the high IgV mutation loads found in all (post) GC B-NHL and why the peak incidence of B-NHL is not early in life, when most primary responses occur, but at late adulthood long after establishing the memory B cell repertoire. In our projects, we aim to analyze, in men and mice, the genetic alterations occurring in B cells upon chronic/intermittent antigenic stimulation. In addition, we aim to develop currently unavailable mouse models for low grade B-cell lymphomas typically found in man.
Ad (II):The transformation of classical adenoma into colorectal cancer (CRC) is well established and viewed as the paradigm for multistep cancer development. It has recently been recognized that lesions previously named hyperplastic polyps, and considered as innocuous, form a heterogeneous group of ‘serrated polyps’ (SP) of which the sessile serrated and traditional serrated adenomas have a significant chance of malignant transformation. Although specific molecular features of SPs have been identified, in particular BRAF mutations and excess of CpG island methylation (CIMP-high) of multiple genes including MLH-1, the pathway to CRC is still obscure. It has been proposed that the group of sporadic, microsatellite-instable (MSI) CRCs originate from SPs. Interestingly, also a hyperplastic polyposis syndrome (HPS) has been recognized, characterized by the presence of multiple SPs in combination with classical adenomas throughout the colon. HPS patients indeed seem to have an increased CRC risk. We intend to (1) identify the genetic defect(s) underlying HPS, (2) identify the somatic gene alterations of sporadic SPs, (3) study the molecular events associated with progression of SP to CRC, in HPS and sporadic patients (4) assess more firmly the relation between the early lesions of the serrated pathway, i.e. the SPs and sporadic MSI and MSS CRC. This work is a collaborative study with the group of Dr. E. Dekkker of the dpt of Gastroenterology and Hepatology.
PhD J.E.J. Guikema
PhD R.J. Bende
- AMC (Vrijgesteld)
- AstraZeneca BV
- Europese Unie
- KWF Kankerbestrijding