I investigate how leukemia stem cells survive and persist in the bone marrow microenvironment to cause relapse. Using a novel 3D spheroid system, I examine the mechanisms behind this persistence to better understand LSC biology and identify potential targets for AML treatment
Leukemia is a cancer of the blood that originates in the bone marrow, where abnormal cells disrupt normal blood production. Among blood cancers, Acute Myeloid Leukemia (AML) is particularly aggressive, as leukemia stem cells (LSCs) drive disease progression and resist chemotherapy, frequently causing relapse. A key reason for this resistance is in the bone marrow microenvironment, where mesenchymal stromal cells (MSCs) shelter LSCs and help maintain their key features, including quiescence and homing to the bone marrow. Current models used to study AML fall short, as liquid cultures, 2D monolayers, and mouse models cannot fully replicate the bone marrow microenvironment. To address this gap, we hypothesized that the novel in vitro 3D spheroid system using MSCs would more accurately replicate the leukemia microenvironment inside the bone marrow compared to traditional models. To test this, AML cells were labeled with CellTrace Violet (CTV) dye and seeded onto MSC-derived spheroids. Colonizing and non-colonizing cell populations were separated and analyzed by flow cytometry. Results showed that a subset of AML cells was capable of successfully colonizing the spheroids, and the colonizing cells displayed higher CTV retention than non-colonizing cells, indicating reduced proliferation, a hallmark of quiescence. These findings suggest that the 3D spheroid system can recreate key conditions of the leukemia bone marrow microenvironment. These results support the use of this model as a more physiologically relevant platform for studying LSC biology. The 3D spheroid system represents a meaningful step toward developing patient-specific avatars for studying LSC biology and identifying targeted AML treatments.
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