Organoids as a new approach in advancing cancer therapies for hematologic malignancies.

Cancer remains one of the leading causes of mortality worldwide. Among these, hematologic malignancies originating in the bone marrow present unique challenges for in vivo modeling due to their complex pathophysiology and dynamic microenvironment. Over the years, numerous approaches have been developed better to understand cancer initiation, progression, and therapeutic resistance. The advent of three-dimensional (3D) organoid culture has accelerated progress in molecular and cellular oncology by providing physiologically relevant models that recapitulate key aspects of human tissues. Derived from pluripotent stem cells or patient-derived samples, organoids replicate essential structural and functional features of native tissues, thereby enabling detailed investigations of disease progression, immune interactions, and treatment responses. This review outlines the historical development and emerging applications of organoid systems in cancer research. Furthermore, introduce hematologic organoids and how bone marrow (BM), lymph nodes (LNs), thymus, and spleen organoids can replicate the hematologic malignancies for personalized therapies and research studies. Additionally, we highlight the influences of key signaling pathways-including Notch, TGF-β, JAK/STAT, and Hedgehog-in regulating hematopoiesis and leukemogenesis within hematologic organoid platforms. Moreover, advances in co-culture systems that integrate tumor cells with stromal and immune components have provided powerful tools for modeling the hematology tumor microenvironment by enhancing preclinical drug testing and introducing personalized therapeutic strategies. As the field advances, the integration of organoid technology with bioengineering approaches and multi-omics platforms is expected to revolutionize translational research and accelerate the development of novel therapies for hematologic cancers.