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

## TL;DR

A new 3D bone marrow model helps study why some B-cell lymphoma treatments fail, offering insights for better personalized therapies.

## Contribution

A high-throughput 3D co-culture system was developed to study drug resistance in B-NHL influenced by the bone marrow microenvironment.

## Key findings

- BM stromal cells reduce lymphoma cell sensitivity to PI3K and BTK inhibitors.
- The 3D platform supports mechanistic studies of microenvironment-driven drug resistance.
- The system could be used for personalized therapeutic strategies in B-NHL.

## 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.