Contribution of the bone marrow stromal cells in mediating drug resistance in hematopoietic tumors

Abstract

The bone marrow microenvironment (BMM) provides input via production of cytokines, chemokines, extracellular matrixes in the context of lower oxygen levels that influences self-renewal, survival, differentiation, progression, and therapeutic resistance of multiple myeloma and leukemic cells. Within the context of the BMM, tumor cells are supported by osteoblasts, bone marrow stromal cells (BMSCs), fibroblasts, myeloid cells, endothelial cells and blood vessels, as well as extracellular matrix (ECM) that contribute to tumor progression. Environmental mediated-drug resistance (EM-DR) contains cell adhesion-mediated drug resistance (CAM-DR) and soluble factor-mediated drug resistance (SM-DR) that contributes to de novo drug resistance. In this review, we focus on the crosstalk between the BMM and tumor cells as well as mechanisms underlying the BMM contributing to drug resistance in hematologic malignancies.