Keck School of Medicine Events
Keck School of Medicine of USC Research Seminar Series
"Adipocytes are Active Participants in Leukemia Progression and Drug Resistance"
Monday, June 3, 2013
11:30 AM - 1:00 PM
Norris Research Towers Aresty Auditorium
Steven D. Mittelman, MD, PhD, Associate Professor with Tenure of Pediatrics and Physiology & Biophysics, Assistant Director, MD/PhD Program,Children's Hospital Los Angeles, Keck School of Medicine of the University of Southern California
Abstract: Obesity increases both the incidence and mortality of numerous types of cancer. Obesity is a complex state, associated with numerous physical, physiological, social, economic, and genetic differences, making it difficult to tease apart the mechanisms linking obesity to cancer. A recent study found that children who are obese at the time of diagnosis of high-risk acute lymphoblastic leukemia (ALL) have a 50% increased risk of relapse compared to lean children. To investigate this, we developed mouse and tissue culture models of obesity and leukemia. We have found that obese mice develop ALL more rapidly, and are more likely to relapse after treatment with first line chemotherapies, even when they are dosed proportional to body weight. Also, we have demonstrated that adipocytes have multiple effects to impair chemotherapy of ALL: they attract leukemia cells, secrete factors which cause ALL resistance to chemotherapy, and they concentrate chemotherapy out of the extracellular environment, making it inaccessible to the ALL cells. Adipocytes also produce important fuels, such as the amino acids asparagines and glutamine, which may help leukemia cells resist certain chemotherapies. These complex effects of adipocytes may help explain why obese individuals have such a substantial increased risk of dying from cancer. Biography Dr. Steven Mittelman is an Associate Professor of Pediatrics and Physiology & Biophysics in the Center for Endocrinology, Diabetes & Metabolism at the Keck School of Medicine, University of Southern California. He received his MD and PhD degrees from the Keck School of Medicine, where he worked on elucidating the physiological mechanisms by which insulin regulates blood sugar in the laboratory of Richard Bergman. Further work examined how pancreatic beta-cells compensate for obesity-induced insulin resistance, and how appetite regulating hormones work in obese adolescents. Steven completed his residency in pediatrics and fellowship in pediatric endocrinology at Children's Hospital Los Angeles. During his subspecialty training, Steven learned of an important finding by researchers in the Children's Center for Cancer and Blood Diseases: children who are obese when they are diagnosed with high-risk leukemia have a 50% higher chance of relapsing than those who are lean. In fact, obesity increases the risk of dying from many different types of cancer, such as breast, colon, and prostate, and may be responsible for up to 15-20% of cancer deaths in the U.S. Dr. Mittelman turned his expertise in obesity into work exploring the relationships between obesity and leukemia relapse, in collaboration with Drs. Nora Heisterkamp and Anna Butturini. His laboratory is currently investigating how obesity and cancer interact, using both mouse models and tissue cultures. Dr. Mittelman is currently investigating strategies to block some of these effects of adipocytes, in the hopes that this will lead to improvements in cancer survival in both thin and overweight people. He is also involved in clinical research, looking at strategies to improve treatment outcome in children with leukemia. In addition to his research, Dr. Mittelman is heavily involved in teaching and mentorship. He currently directs the Endocrinology Fellowship at CHLA, and is the Associate Director of the MD/PhD Program at the Keck School of Medicine. He is also the founding director of the George Donnell Society for Pediatric Scientists at Children's Hospital Los Angeles, which is dedicated to training the next generation of pediatric physician scientists.
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