Current efforts in translational studies in hematology often rely on immunodeficient mouse models for engrafting patient-derived hematopoietic stem and progenitor cells (HSPCs), yet these models often face challenges in effectively engrafting cells from patients with various diseases, such as myelodysplastic syndromes (MDSs). In this study, we developed an induced pluripotent stem cell (iPSC)-derived human bone marrow organoid model that closely replicates the bone marrow microenvironment, facilitating the engraftment of HSPCs derived from patients with MDS, thereby mirroring the patients' distinct disease characteristics. Specifically, using advanced microscopy, we verified the development of a complex 3-dimensional network of endothelial, stromal, and hematopoietic cells within organoids, resembling the autonomous human marrow microenvironment. Furthermore, we showed that HSPCs derived from the donor bone marrow of normal individuals or patients with MDS can migrate to and proliferate within the organoid vascular niche while maintaining self-renewal and original genetic profiles. Within the organoids, the differentiation patterns of MDS HSPCs were significantly distinct from those of multilineage hematopoiesis in normal HSPCs, which can be correlated with the clinical manifestations of the disease. These findings underscore the significance of the organoid model in studying human hematopoiesis and the pathophysiology of hematologic diseases, thereby offering new avenues for personalized medicine and therapeutic interventions.