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Modeling the Leukemia Microenviroment In Vitro

Over the last decade, the active role of the microenvironment in the pathogenesis, development and drug resistance of B cell malignancies has been clearly established. It is known that the tissue microenvironment promotes proliferation and drug resistance of leukemic cells suggesting that successful...

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Autores principales: Scielzo, Cristina, Ghia, Paolo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7773937/
https://www.ncbi.nlm.nih.gov/pubmed/33392097
http://dx.doi.org/10.3389/fonc.2020.607608
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author Scielzo, Cristina
Ghia, Paolo
author_facet Scielzo, Cristina
Ghia, Paolo
author_sort Scielzo, Cristina
collection PubMed
description Over the last decade, the active role of the microenvironment in the pathogenesis, development and drug resistance of B cell malignancies has been clearly established. It is known that the tissue microenvironment promotes proliferation and drug resistance of leukemic cells suggesting that successful treatments of B cell malignancies must target the leukemic cells within these compartments. However, the cross-talk occurring between cancer cells and the tissue microenvironment still needs to be fully elucidated. In solid tumors, this lack of knowledge has led to the development of new and more complex in vitro models able to successfully mimic the in vivo settings, while only a few simplified models are available for haematological cancers, commonly relying only on the co-culture with stabilized stromal cells and/or the addition of limited cocktails of cytokines. Here, we will review the known cellular and molecular interactions occurring between monoclonal B lymphocytes and their tissue microenvironment and the current literature describing innovative in vitro models developed in particular to study chronic lymphocytic leukemia (CLL). We will also elaborate on the possibility to further improve such systems based on the current knowledge of the key molecules/signals present in the microenvironment. In particular, we think that future models should be developed as 3D culture systems with a higher level of cellular and molecular complexity, to replicate microenvironmental-induced signaling. We believe that innovative 3D-models may therefore improve the knowledge on pathogenic mechanisms leading to the dissemination and homing of leukemia cells and consequently the identification of therapeutic targets.
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spelling pubmed-77739372021-01-01 Modeling the Leukemia Microenviroment In Vitro Scielzo, Cristina Ghia, Paolo Front Oncol Oncology Over the last decade, the active role of the microenvironment in the pathogenesis, development and drug resistance of B cell malignancies has been clearly established. It is known that the tissue microenvironment promotes proliferation and drug resistance of leukemic cells suggesting that successful treatments of B cell malignancies must target the leukemic cells within these compartments. However, the cross-talk occurring between cancer cells and the tissue microenvironment still needs to be fully elucidated. In solid tumors, this lack of knowledge has led to the development of new and more complex in vitro models able to successfully mimic the in vivo settings, while only a few simplified models are available for haematological cancers, commonly relying only on the co-culture with stabilized stromal cells and/or the addition of limited cocktails of cytokines. Here, we will review the known cellular and molecular interactions occurring between monoclonal B lymphocytes and their tissue microenvironment and the current literature describing innovative in vitro models developed in particular to study chronic lymphocytic leukemia (CLL). We will also elaborate on the possibility to further improve such systems based on the current knowledge of the key molecules/signals present in the microenvironment. In particular, we think that future models should be developed as 3D culture systems with a higher level of cellular and molecular complexity, to replicate microenvironmental-induced signaling. We believe that innovative 3D-models may therefore improve the knowledge on pathogenic mechanisms leading to the dissemination and homing of leukemia cells and consequently the identification of therapeutic targets. Frontiers Media S.A. 2020-12-17 /pmc/articles/PMC7773937/ /pubmed/33392097 http://dx.doi.org/10.3389/fonc.2020.607608 Text en Copyright © 2020 Scielzo and Ghia http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Oncology
Scielzo, Cristina
Ghia, Paolo
Modeling the Leukemia Microenviroment In Vitro
title Modeling the Leukemia Microenviroment In Vitro
title_full Modeling the Leukemia Microenviroment In Vitro
title_fullStr Modeling the Leukemia Microenviroment In Vitro
title_full_unstemmed Modeling the Leukemia Microenviroment In Vitro
title_short Modeling the Leukemia Microenviroment In Vitro
title_sort modeling the leukemia microenviroment in vitro
topic Oncology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7773937/
https://www.ncbi.nlm.nih.gov/pubmed/33392097
http://dx.doi.org/10.3389/fonc.2020.607608
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