Prof. dr. C.J.M. van Noesel

Main activities
Patient care, Research
Focus of research

B cel biology and the pathogenesis of B cel non-Hodgkin lymphomas

The serrated neoplasia pathway to colorectal cancer

Key publications
  • Bende RJ, Aarts WM, Riedl RG, de Jong D, Pals ST, van Noesel CJM, Among B cell non-Hodgkin's lymphomas, MALT lymphomas express a unique antibody repertoire with frequent rheumatoid factor reactivity. J EXP MED 2005;201 (8):1229-1241 [PubMed]
  • Bende RJ, van Maldegem F, Triesscheijn M, Wormhoudt TAM, Guijt R, van Noesel CJM, Germinal centers in human lymph nodes contain reactivated memory B cells. J EXP MED 2007;204 (11):2655-2665 [PubMed]
  • Hoogeboom R, van Kessel KPM, Hochstenbach F, Wormhoudt TA, Reinten RJA, Wagner K, Kater AP, Guikema JEJ, Bende RJ, van Noesel CJM, A mutated B cell chronic lymphocytic leukemia subset that recognizes and responds to fungi. J EXP MED 2013;210 (1):59-70 [PubMed]
  • Boparai KS, Dekker E, van Eeden S, Polak MM, Bartelsman JFWM, Mathus-Vliegen EMH, Keller JJ, van Noesel CJM, Hyperplastic polyps and sessile serrated adenomas as a phenotypic expression of MYH-associated polyposis. GASTROENTEROLOGY 2008;135 (6):2014-2018 [PubMed]
  • Boparai KS, Dekker E, Polak MM, Musler AR, van Eeden S, van Noesel CJM, A Serrated Colorectal Cancer Pathway Predominates over the Classic WNT Pathway in Patients with Hyperplastic Polyposis Syndrome. AM J PATHOL 2011;178 (6):2700-2707 [PubMed]
All Publications
Research programmes

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.

Prof. dr. C.J.M. van Noesel
J.E.J. Guikema PhD

Dr. R.J. Bende PhD

PhD Students
Drs. T.A. Bloedjes
N. Donner
J. Janssen
Drs. K. Mackovicova
Drs. L. Slot
G. Wilde

Ing. T.A.M. Wormhoudt

Current research funding
  • AMC
  • AMC (Vrijgesteld)
  • Europese Unie
  • KWF Kankerbestrijding
  • Stichting KIKA
  • Stichting ReumaNederland