A high‐throughput bone marrow <scp>3D</scp> co‐culture system to study resistance to <scp>BCR</scp> signalling targeted agents in B‐ <scp>NHL</scp>

Bone marrow (BM) involvement in B-cell non-Hodgkin lymphoma (B-NHL) is associated with poor prognosis, as the BM microenvironment provides a protective niche that promotes therapeutic resistance. We developed a simplified, automated and high-throughput 3D BM co-culture model that faithfully reproduces key tumour-stroma interactions. In our system, BM stromal cells (BMSCs) decreased lymphoma cell sensitivity to Phosphatidylinositol 3-kinase (PI3K) and BTK inhibitors. Moreover, we show that our 3D platform enables the mechanistic studies of microenvironment-mediated drug resistance and has the potential to be developed into a tool for personalized therapeutic strategies for B-NHL.

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Publication Details

Journal
British Journal of Haematology
Published
2025-12-08
DOI
https://doi.org/10.1111/bjh.70273
Primary Topic
Lymphoma Diagnosis and Treatment
Type
article
Field-Weighted Citation Impact
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article

A high‐throughput bone marrow 3D co‐culture system to study resistance to BCR signalling targeted agents in B‐ NHL

Matteo Moretti, Christian Candrian, Alberto J. Arribas, Afua A. Mensah et al.
British Journal of Haematology
Lymphoma Diagnosis and Treatment
article

A high‐throughput bone marrow 3D co‐culture system to study resistance to BCR signalling targeted agents in B‐ NHL

Matteo Moretti, Christian Candrian, Alberto J. Arribas, Afua A. Mensah, Filippo Spriano, Eleonora Cannas, Chiara Arrigoni, Maria Vittoria Colombo, Francesco Bertoni, Dalila Petta, Federico Simonetta, Luciano Cascione, Alex Zadro
article en

Abstract

Bone marrow (BM) involvement in B-cell non-Hodgkin lymphoma (B-NHL) is associated with poor prognosis, as the BM microenvironment provides a protective niche that promotes therapeutic resistance. We developed a simplified, automated and high-throughput 3D BM co-culture model that faithfully reproduces key tumour-stroma interactions. In our system, BM stromal cells (BMSCs) decreased lymphoma cell sensitivity to Phosphatidylinositol 3-kinase (PI3K) and BTK inhibitors. Moreover, we show that our 3D platform enables the mechanistic studies of microenvironment-mediated drug resistance and has the potential to be developed into a tool for personalized therapeutic strategies for B-NHL.

British Journal of HaematologyVol. 208(2)
University of Geneva (CH), SIB Swiss Institute of Bioinformatics (CH), Swiss Institute for Regenerative Medicine (CH), Ente Ospedaliero Cantonale (CH), Institute of Oncology Research (CH), University Hospital of Geneva (CH), IRCCS Ospedale Galeazzi - Sant'Ambrogio (IT), Istituto Oncologico della Svizzera Italiana, Università della Svizzera italiana (CH), Geneva College (US)
Openalex Percentile: Top 45%
Lymphoma Diagnosis and Treatment
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