A <scp>3D</scp> Bioprinted Platform That Maintains the Functional Integrity of Primary <scp>AML</scp> Cells

Acute myeloid leukaemia (AML) urgently requires more reliable in vitro platforms for drug evaluation, as existing models often fail to maintain the phenotypic, metabolic, and pharmacologic features of primary leukaemic cells. To address this limitation, we developed a rapidly assembled, screening-compatible three-dimensional (3D) bioprinting platform. It encapsulates patient-derived bone marrow mononuclear cells within a gelatin-hyaluronic acid hydrogel, whose mechanical properties are tuned to match those of native bone marrow. Within this controlled 3D microenvironment, primary AML cells better maintain an in vivo-like state, showing enhanced viability, sustained proliferative capacity, preservation of stem-like subpopulations, and drug responses that more closely mirror clinical behaviour. Transcriptomic profiling further revealed robust activation of MYC target programs and mTORC1 signalling, accompanied by elevated oxidative phosphorylation and glycolytic activity, indicative of the highly proliferative and metabolically active state exhibited by AML cells in vivo. These findings demonstrate that our patient-specific, 3D bioprinted system provides a high-fidelity model. This model faithfully recapitulates AML physiology and metabolic features while capturing inter-patient variability. Consequently, it offers a more reliable and predictive platform for preclinical drug assessment.