Models to study myelodysplastic syndrome and acute myeloid leukaemia

Purpose of review: Myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML) are hematological malignancies characterized by complex genetic alterations, leading to poor clinical outcomes. Despite advances in treatment, there is an urgent need for novel therapeutic approaches. This review outlines recent progress in humanized models of MDS and AML and highlight their role in advancing our understanding of these diseases.

Recent findings: Patient derived xenografts (PDXs) were among the first humanized models for studying MDS and AML, allowing researchers to analyze patient-specific cancer properties in vivo. However, they face challenges related to sample availability and consistent engraftment in mice. New methods, including specialized mouse strains and human tissue scaffolds, have been developed to address these issues. Induced pluripotent stem cells (iPSCs) offer the advantage of indefinite expansion and genetic modification, making them valuable for in vitro research, though protocols to enhance their engraftment in vivo are still being refined. Genetically engineered human primary hematopoietic stem and progenitor cells (HSPCs) provide reliable in vivo models with good engraftment in mice, and recent advancements in culture systems and gene-editing techniques are helping to overcome challenges related to ex vivo expansion and genetic modification.

Summary: PDXs, iPSCs, and genetically engineered HSPCs are crucial models for the study of MDS and AML. This review discusses strengths, limitations, and recent advancements of these humanized models, which provide insights into human-specific disease biology and therapeutic development.