Early stages in the ontogeny of small B-cell lymphomas: genetics and microenvironment
Early stages in the ontogeny of small B-cell lymphomas: genetics and microenvironment
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.
Humans, Leukemia, Lymphocytic, Chronic, B-Cell, Lymphoma, Follicular, Lymphoma, Mantle-Cell, Splenic Neoplasms, Tumor Microenvironment, Journal Article, Review
395-414
Ghia, P.
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Nadel, B.
5d0d5168-66bc-4c29-b7a6-7e2f0c6d8760
Sander, B.
954c740a-8d28-4e93-9964-7dc5f8a9877a
Stamatopoulos, K.
a36ff638-a62a-4a89-bb5a-623e7ea653fe
Stevenson, F.K.
ba803747-c0ac-409f-a9c2-b61fde009f8c
November 2017
Ghia, P.
f05ed1e5-7dec-43a5-afa5-b2e83a448f13
Nadel, B.
5d0d5168-66bc-4c29-b7a6-7e2f0c6d8760
Sander, B.
954c740a-8d28-4e93-9964-7dc5f8a9877a
Stamatopoulos, K.
a36ff638-a62a-4a89-bb5a-623e7ea653fe
Stevenson, F.K.
ba803747-c0ac-409f-a9c2-b61fde009f8c
Ghia, P., Nadel, B., Sander, B., Stamatopoulos, K. and Stevenson, F.K.
(2017)
Early stages in the ontogeny of small B-cell lymphomas: genetics and microenvironment.
Journal of Internal Medicine, 282 (5), .
(doi:10.1111/joim.12608).
Abstract
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.
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Accepted/In Press date: 1 April 2016
e-pub ahead of print date: 10 April 2017
Published date: November 2017
Keywords:
Humans, Leukemia, Lymphocytic, Chronic, B-Cell, Lymphoma, Follicular, Lymphoma, Mantle-Cell, Splenic Neoplasms, Tumor Microenvironment, Journal Article, Review
Identifiers
Local EPrints ID: 416079
URI: http://eprints.soton.ac.uk/id/eprint/416079
ISSN: 0954-6820
PURE UUID: d72717cb-5890-4750-b587-70b4bb2f4867
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Date deposited: 01 Dec 2017 17:30
Last modified: 16 Mar 2024 02:54
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Author:
P. Ghia
Author:
B. Nadel
Author:
B. Sander
Author:
K. Stamatopoulos
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