Washington University in St. Louis
Project Term: July 1, 2017 - June 30, 2022
My research is focused on understanding how a protein, CXCR4, promotes the growth and survival of T-cell acute lymphoblastic leukemia. We are conducting a clinical trial in patients with T-ALL to test if a CXCR4 inhibitor, BL-8040, can increase the effectiveness of chemotherapy. Additional studies seek to understand how BL-8040 causes the death of tumor cells and to test novel agents in combination with BL-8040 with an overall goal of improving clinical outcomes in T-ALL.
T-cell acute lymphoblastic leukemia (T-ALL) is a subtype which comprises about 20% of all cases of acute lymphoblastic leukemia. T-ALL is a particularly rare disease in adults, with only about 600 new cases per year in the United States. Furthermore, the prognosis of adults is poor; only 40% of adults with T-ALL are cured with current treatments. Our laboratory work has demonstrated that T-ALL cells interact with normal cells present in their local environment (called the “microenvironment”), which provides key signals that regulate tumor growth and survival. Our research has focused on a specific protein, CXCR4, which is present in T-ALL cells. In T-ALL, the tumor microenvironment provides a potent growth and survival signal, which is mediated by CXCR4, to T-ALL. We hypothesize that it is possible to disrupt this tumor-microenvironmental interaction as a means to treat T-ALL patients. We will disrupt the key survival signal to T-ALL cells using a novel inhibitor of CXCR4 known as BL-8040. We are currently conducting a multicenter study to combine BL-8040 treatment with chemotherapy in patients with T-ALL that has relapsed or is refractory to standard treatments. As part of this study, we will test blood and bone marrow samples from patients after treatment to determine the effects of BL-8040 on leukemia cells. We will also conduct additional preclinical studies to test the effects of new combinations of drugs to improve the effectiveness of BL-8040. The overall goal of this project is to target tumor-microenvironment interactions to improve the outcomes of patients with T-ALL.