Defining the Extracellular Matrix Composition of the Acute Myeloid Leukemia Cell Niche: Towards Development of a Functional 3D Drug Screening System

Acute Myeloid Leukemia is a heterogeneous hematopoietic malignancy, which has been shown to modify the bone marrow microenvironment towards cooperating with the cancer cell to promote their proliferation. In this research I optimized a procedure for growing AML cells in a novel culture system in vitro in order to provide the cells with a microenvironment more closely resembling the native cell niche. Next, an analysis of various ECM components was undertaken to assess whether their presence may affect AML cell survival. In a proof-of-concept study, I employed the novel culture system to analyze the effect of 160 chemical agents on cell survival and compared the traditional polystyrene cultures with the novel 2D and 3D collagen culture systems. By recapitulating the tumor microenvironment with three-dimensional collagen scaffolds, I was able to demonstrate a microenvironment-dependent variation in drug response and identify novel targets that may not have been detected with a traditional screening assay