Our laboratory is interested in understanding the links between obesity and cancer mortality. Studies have shown that obese people have a substantially higher risk of dying from cancer than nonobese individuals. However, the reasons for this association are not fully understood. Obese children who are diagnosed with the most common childhood cancer, acute lymphoblastic leukemia (ALL), have a ~50% higher risk of leukemia relapse after treatment than nonobese children. Our lab is committed to understanding why these children have a poorer outcome, and developing strategies to reverse this effect. Our research has spans the translational gamut, including cell culture, preclinical models, clinical studies, and epidemiology.
Dr. Mittelman is a member of the Metabolism Theme
ALL cells in adipose tissue: Picture shows green GFP+ ALL cells infiltrating into adipose tissue of a mouse after chemotherapy treatment
Using mouse and tissue culture models, we have shown that obesity directly impacts the progression and treatment outcome of ALL. Mice which are prone to develop ALL do so earlier when they are made obese with a high-fat diet. Further, obese mice with leukemia have a poorer response to chemotherapy. We have found that fat cells protect ALL cells from multiple chemotherapies, through a variety of mechanisms. Because fat cells are found in the bone marrow, which is generally accepted to be a protective microenvironmental niche of ALL cells, this protection could contribute to poorer outcomes in patients. Further, we discovered that adipocytes attract ALL cells through chemokine secretion, which could result in ALL cells migrating into adipose tissue where they are protected from chemotherapy and can act as a reservoir for relapsing ALL cells. We are working to understand the two-way communications between ALL cells and adipocytes, and explore strategies to block these effects.