Study the Activity of Small Molecule Inhibitor AI-10-49 in Combined Treatment of Childhood Inv(16) AML

Background

The treatment of childhood acute myeloid leukemia (AML) is based on the use of high dose chemotherapies, with significant toxicity and varied prognosis. The emergence of targeted therapy strategies in cancer treatment has enlightened the hope for developing new drugs with higher potency and reduced toxicity in patients.

The Castilla laboratory focuses on understanding how mutations found in AML cells disrupt the function of normal blood cells. These studies have identified specific processes in the cells, which dominate in the leukemic cells. The Castilla laboratory helped develop a new molecule, called A-10-49, which eliminates the leukemic cell with a specific mutation while sparing the normal cells toxicity. The use of AI-10-49 could be best when used as combination therapy.

Project Goal

The goal of this study is to test if using AI-10-49 with another drug at lower concentrations would potentiate their anti-leukemia function and minimize the toxicity. I will evaluate the ability of AI-10-49 and different concentrations of a panel of 12 leukemia drugs to induce death of the leukemia cells but not of normal cells. The identification of combination therapy drugs in leukemia cells would serve as the foundation for follow up studies in mouse leukemia models and patient-derived cells.