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GelMA-based 3D spheroids recapitulate transcriptomic and functional hallmarks of myeloid sarcoma
Nicolas Germain1,2, Elise Buret1, Le Hoang Thanh Nguyen1
1University of Lille, CNRS, Inserm, CHU Lille, Institut de Recherche Contre le Cancer de Lille, UMR9020 - UMR-S 1277 - Canther Cancer Heterogeneity, Plasticity and Therapy Resistance, France.
This study introduces a 3D hydrogel model for myeloid sarcoma (MS), an extramedullary manifestation of acute myeloid leukemia (AML). This innovative platform accurately mimics the MS microenvironment, aiding in understanding disease biology and therapeutic development.
Area of Science:
- Biomedical Engineering
- Cancer Biology
- Hematology
Background:
- Myeloid sarcoma (MS) is a rare extramedullary form of acute myeloid leukemia (AML).
- Conventional 2D cell cultures do not accurately represent the complex in vivo microenvironment of MS.
- There is a need for advanced in vitro models to study MS biology and test therapies.
Purpose of the Study:
- To develop and validate a tunable 3D in vitro model for studying myeloid sarcoma.
- To investigate the impact of a 3D microenvironment on leukemia cell behavior and gene expression.
- To establish a clinically relevant platform for MS research.
Main Methods:
- Utilized 5% gelatin methacrylate (GelMA) hydrogels as a tunable 3D matrix.
- Cultured myeloid leukemia cell lines within GelMA hydrogels to form spheroids.
- Assessed spheroid viability, cell cycle progression, apoptosis, and gene expression via RNA sequencing.
- Compared transcriptomic profiles of 3D-cultured cells with patient-derived MS samples.
Main Results:
- GelMA hydrogels provided tissue-like stiffness and controlled oxygen diffusion, supporting viable spheroid formation.
- The 3D environment induced G1 cell cycle arrest and apoptosis, mimicking extramedullary MS dormancy.
- RNA sequencing revealed significant transcriptional reprogramming, including enrichment of ECM remodeling and metabolic pathways.
- Transcriptomic data from the 3D model closely aligned with patient-derived MS samples, validating the model.
Conclusions:
- A GelMA-based 3D hydrogel system offers a clinically relevant platform for modeling myeloid sarcoma.
- This model recapitulates key aspects of MS biology, including cell dormancy and transcriptional changes.
- The developed system is suitable for investigating MS pathogenesis and screening novel therapeutic strategies.
