Beneficial impact of bone marrow supportive tissues on acute lymphoblastic leukemia

The bone marrow microenvironment (BME) facilitates leukemogenesis and therapy resistance. Studies into the relation of BCP-ALL and the BME have mostly been focused on the role of mesenchymal stromal cells (MSCs). We aim to understand which other stromal tissue types also give (prolonged) support to patients’ BCP-ALL cells, to develop a representative ex vivo BME model, enabling functional studies. All tested supportive cell types provided ex vivo survival benefit to BCP-ALL cells with a median benefit of 18-24% (chondrocytes and early adipocytes) and 30-36% (MSCs and osteocytes). Exposure of leukemic cells to a mixture of supportive tissue types in a 3D microfluidics model induced increased cell proliferation compared with leukemic cells co-cultured with each of the individual supportive cell types separately. Our data suggest that BCP-ALL cells manipulate different components of the bone marrow supportive tissues similarly, favoring survival of leukemic cells and creating a pro-inflammatory microenvironment. Current studies are addressing the impact of a leukemic BME on the efficacy of cellular immunotherapies like blinatumomab and CAR-T.

Publication History

Article published online:
09 May 2025