Targeting microenvironment-induced TGFB signaling to overcome drug resistance in acute lymphoblastic leukemia
This grant supported research to understand how the bone marrow microenvironment influence the response of acute lymphoblastic leukemia cells to drug treatment. We used multiple laboratory approaches and identified multiple new proteins and cellular pathways that mediate drug resistance. We also identified a population of leukemia cells that acquire stromal-like properties on engagement with bone marrow stroma. We used this information ro identify and validate a new therapeutic approach to overcome resistance, which is potentially translatable to the clinic. It is not known YET if this will translate to a clinical trial.
This project will examine the role of tumor microenvironment in drug resistance of ALL. To understand the mechanism of ALL-microenvironment interaction, we will use single cell genomic and proteomic tools to characterize the molecules and signaling pathways that are mis-regulated when ALL cells interact with the microenvironment. This will lead to the development of novel therapies that reverse adherence and increase sensitivity to cytotoxic drugs. Overall this study will provide a rationale to guide the development of clinical trials testing new agents to overcome resistance and improve overall survival of this disease.