Cargando…

Bone Marrow Stromal Cells Drive Key Hallmarks of B Cell Malignancies

All B cell leukaemias and a substantial fraction of lymphomas display a natural niche residency in the bone marrow. While the bone marrow compartment may only be one of several sites of disease manifestations, the strong clinical significance of minimal residual disease (MRD) in the bone marrow stro...

Descripción completa

Detalles Bibliográficos
Autores principales: Mangolini, Maurizio, Ringshausen, Ingo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7073037/
https://www.ncbi.nlm.nih.gov/pubmed/32098106
http://dx.doi.org/10.3390/ijms21041466
_version_ 1783506545165729792
author Mangolini, Maurizio
Ringshausen, Ingo
author_facet Mangolini, Maurizio
Ringshausen, Ingo
author_sort Mangolini, Maurizio
collection PubMed
description All B cell leukaemias and a substantial fraction of lymphomas display a natural niche residency in the bone marrow. While the bone marrow compartment may only be one of several sites of disease manifestations, the strong clinical significance of minimal residual disease (MRD) in the bone marrow strongly suggests that privileged niches exist in this anatomical site favouring central elements of malignant transformation. Here, the co-existence of two hierarchical systems, originating from haematopoietic and mesenchymal stem cells, has extensively been characterised with regard to regulation of the former (blood production) by the latter. How these two systems cooperate under pathological conditions is far less understood and is the focus of many current investigations. More recent single-cell sequencing techniques have now identified an unappreciated cellular heterogeneity of the bone marrow microenvironment. How each of these cell subtypes interact with each other and regulate normal and malignant haematopoiesis remains to be investigated. Here we review the evidences of how bone marrow stroma cells and malignant B cells reciprocally interact. Evidently from published data, these cell–cell interactions induce profound changes in signalling, gene expression and metabolic adaptations. While the past research has largely focussed on understanding changes imposed by stroma- on tumour cells, it is now clear that tumour-cell contact also has fundamental ramifications for the biology of stroma cells. Their careful characterisations are not only interesting from a scientific biological viewpoint but also relevant to clinical practice: Since tumour cells heavily depend on stroma cells for cell survival, proliferation and dissemination, interference with bone marrow stroma–tumour interactions bear therapeutic potential. The molecular characterisation of tumour–stroma interactions can identify new vulnerabilities, which could be therapeutically exploited.
format Online
Article
Text
id pubmed-7073037
institution National Center for Biotechnology Information
language English
publishDate 2020
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-70730372020-03-19 Bone Marrow Stromal Cells Drive Key Hallmarks of B Cell Malignancies Mangolini, Maurizio Ringshausen, Ingo Int J Mol Sci Review All B cell leukaemias and a substantial fraction of lymphomas display a natural niche residency in the bone marrow. While the bone marrow compartment may only be one of several sites of disease manifestations, the strong clinical significance of minimal residual disease (MRD) in the bone marrow strongly suggests that privileged niches exist in this anatomical site favouring central elements of malignant transformation. Here, the co-existence of two hierarchical systems, originating from haematopoietic and mesenchymal stem cells, has extensively been characterised with regard to regulation of the former (blood production) by the latter. How these two systems cooperate under pathological conditions is far less understood and is the focus of many current investigations. More recent single-cell sequencing techniques have now identified an unappreciated cellular heterogeneity of the bone marrow microenvironment. How each of these cell subtypes interact with each other and regulate normal and malignant haematopoiesis remains to be investigated. Here we review the evidences of how bone marrow stroma cells and malignant B cells reciprocally interact. Evidently from published data, these cell–cell interactions induce profound changes in signalling, gene expression and metabolic adaptations. While the past research has largely focussed on understanding changes imposed by stroma- on tumour cells, it is now clear that tumour-cell contact also has fundamental ramifications for the biology of stroma cells. Their careful characterisations are not only interesting from a scientific biological viewpoint but also relevant to clinical practice: Since tumour cells heavily depend on stroma cells for cell survival, proliferation and dissemination, interference with bone marrow stroma–tumour interactions bear therapeutic potential. The molecular characterisation of tumour–stroma interactions can identify new vulnerabilities, which could be therapeutically exploited. MDPI 2020-02-21 /pmc/articles/PMC7073037/ /pubmed/32098106 http://dx.doi.org/10.3390/ijms21041466 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Review
Mangolini, Maurizio
Ringshausen, Ingo
Bone Marrow Stromal Cells Drive Key Hallmarks of B Cell Malignancies
title Bone Marrow Stromal Cells Drive Key Hallmarks of B Cell Malignancies
title_full Bone Marrow Stromal Cells Drive Key Hallmarks of B Cell Malignancies
title_fullStr Bone Marrow Stromal Cells Drive Key Hallmarks of B Cell Malignancies
title_full_unstemmed Bone Marrow Stromal Cells Drive Key Hallmarks of B Cell Malignancies
title_short Bone Marrow Stromal Cells Drive Key Hallmarks of B Cell Malignancies
title_sort bone marrow stromal cells drive key hallmarks of b cell malignancies
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7073037/
https://www.ncbi.nlm.nih.gov/pubmed/32098106
http://dx.doi.org/10.3390/ijms21041466
work_keys_str_mv AT mangolinimaurizio bonemarrowstromalcellsdrivekeyhallmarksofbcellmalignancies
AT ringshauseningo bonemarrowstromalcellsdrivekeyhallmarksofbcellmalignancies