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Early stages in the ontogeny of small B-cell lymphomas: genetics and microenvironment
Univ Vita Salute San Raffaele, Div Expt Oncol, Milan, Italy.;IRCCS San Raffaele Sci Inst Milan, Milan, Italy..
Aix Marseille Univ, CNRS, INSERM, CIML, Marseille, France..
Karolinska Inst, Dept Lab Med, Div Pathol, Stockholm, Sweden.;Karolinska Univ Hosp, SE-14186 Stockholm, Sweden..
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology. Ctr Res & Technol Hellas, Inst Appl Biosci, Thessaloniki, Greece.
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2017 (English)In: Journal of Internal Medicine, ISSN 0954-6820, E-ISSN 1365-2796, Vol. 282, no 5, p. 395-414Article in journal (Refereed) Published
Abstract [en]

In this review, we focus on the mechanisms underlying lymphomagenesis in chronic lymphocytic leukaemia, follicular lymphoma, mantle cell lymphoma and splenic marginal zone lymphoma. The cells of origin of these small B-cell lymphomas are distinct, as are the characteristic chromosomal lesions and clinical courses. One shared feature is retention of expression of surface immunoglobulin. Analysis of this critical receptor reveals the point of differentiation reached by the cell of origin. Additionally, the sequence patterns of the immunoglobulin-variable domains can indicate a role for stimulants of the B-cell receptor before, during and after malignant transformation. The pathways driven via the B-cell receptor are now being targeted by specific kinase inhibitors with exciting clinical effects. To consider routes to pathogenesis, potentially offering earlier intervention, or to identify causative factors, genetic tools are being used to track pretransformation events and the early phases in lymphomagenesis. These methods are revealing that chromosomal changes are only one of the many steps involved, and that the influence of surrounding cells, probably multiple and variable according to tissue location, is required, both to establish tumours and to maintain growth and survival. Similarly, the influence of the tumour microenvironment may protect malignant cells from eradication by treatment, and the resulting minimal residual disease will eventually give rise to relapse. The common and different features of the four lymphomas will be summarized to show how normal B lymphocytes can be subverted to generate tumours, how these tumours evolve and how their weaknesses can be attacked by targeted therapies.

Place, publisher, year, edition, pages
2017. Vol. 282, no 5, p. 395-414
Keywords [en]
chronic lymphocytic leukaemia, follicular lymphoma, lymphomagenesis, mantle cell lymphoma, microenvironment, splenic marginal zone lymphoma
National Category
Cancer and Oncology
Identifiers
URN: urn:nbn:se:uu:diva-339736DOI: 10.1111/joim.12608ISI: 000413307000004PubMedID: 28393412OAI: oai:DiVA.org:uu-339736DiVA, id: diva2:1177796
Conference
Symposium on Targeted Therapy in B-Cell Malignancies, SEP 29-30, 2016, Karolinska Inst, Stockholm, SWEDEN
Available from: 2018-01-26 Created: 2018-01-26 Last updated: 2018-01-26Bibliographically approved

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