Bioengineered In vitro bone marrow models of acute myeloid leukemia for novel drug discovery.

INTRODUCTION: Acute myeloid leukemia (AML) is an aggressive hematological malignancy associated with poor prognosis, high rates of chemoresistance and disease relapse. High attrition rates in the drug development pipeline highlight the need for improved modeling strategies that provide more reliable translation from preclinical to clinical outcomes. Bioengineered human cell-based bone marrow models are emerging as promising platforms capable of recapitulating key aspects of disease biology and therapeutic response more faithfully than conventional models. AREAS COVERED: This review discusses advances in bioengineered bone marrow models of AML, including systems capable of reproducing chemoresistance, off-target toxicities, leukemic niche remodeling, and microenvironment-mediated disease mechanisms that are often overlooked by conventional two-dimensional cultures and current animal models. The physical, cellular, and biochemical properties to be considered in next-generation models are also examined. Literature was identified through searches of PubMed, Science Direct, and Google Scholar. EXPERT OPINION: Bioengineered AML bone marrow models have the potential to improve drug development by identifying ineffective compounds earlier and enabling investigation of patient-specific disease heterogeneity. Future progress will depend not only on increasing biological complexity through technologies such as organoids and organ-on-chip systems, but also on rigorous validation against patient data, standardization, scalability, and regulatory acceptance.