Obesity linked to increased risk of leukemia
Obesity is of epidemic proportions throughout the US. In addition to cardiovascular disease and diabetes, researchers are continuing to discover more ways that obesity can damage the body. These include altering an individual’s ability to smell, disrupting sleep and sexual function, and accelerating cancerous tumor growth. Obesity in children is also linked to serious health problems.
Fat cells produce numerous hormones, inflammatory molecules and other chemicals that can act directly on nearby organs or travel to cause damage in other areas of the body. Better understanding how this works might eventually open new avenues for treatment of obesity and linked conditions. The soaring obesity rate among children is particularly disturbing. To gain further insight into this problem, I interviewed Steven Mittelman, MD, PhD in regard to his research on the connection between leukemia (a type of blood cancer) and obesity in children. He is a pediatric endocrinologist affiliated with Children’s Hospital Los Angeles and the Keck School of Medicine of the University of Southern California. His research, funded by a grant from the Gabrielle’s Angel Foundation for Cancer Research, has discovered that fat cells protect leukemia cells from a variety of chemotherapies, along with the fact that obesity accelerates the progression of leukemia. Obese children, when diagnosed with the most common type of childhood leukemia have about a 50% higher chance of their disease relapsing after treatment than patients who were lean.
Overweight individuals have an increased risk of developing and dying from cancer. Harold Varmus, the Director of the National Cancer Institute, recently said that “On the order of 20% of cancers in this country would not occur if we didn’t have such an obese population” Studies at Children’s Hospital Los Angeles found that children and adults who were very overweight when they were diagnosed with leukemia had a 50% higher risk of their disease coming back after treatment than lean patients. Dr. Mittelman notes that his laboratory has investigated how being overweight might affect leukemia treatment. His research tem previously found that obesity accelerates leukemia progression, and fat cells directly impair leukemia treatment.
Using overweight and lean preclinical models (laboratory studies), the researchers found that the important leukemia treatment, L-asparaginase, is less effective in the overweight state. In cell culture, we found that fat cells themselves can block the effect of L-asparaginase to kill leukemia cells. Since L-asparaginase acts by breaking down the important amino acids asparagine and glutamine, we are investigating whether fat cells protect leukemia from this drug by producing these amino acids.
They have found that fat cells from preclinical models can in fact produce glutamine, and that this fuel seems to protect leukemia cells from L-asparaginase. Dr. Mittelman notes that his team has examined some bone marrow specimens from children with leukemia, and found that the fat cells in the bone marrow increase the amount of the enzyme that makes glutamine during the initial courses of chemotherapy. In addition, they have found that another form of L-asparaginase, which is more capable of lowering glutamine levels, is more able to kill leukemia cells even when fat cells are present in culture.
These findings together show that fat cell production of glutamine may indeed be responsible for blocking L-asparaginase in patients with leukemia, and could contribute to the effect of obesity to increase the chance of leukemia coming back after treatment. They also provided justification for testing other forms of asparaginase which are better at suppressing glutamine levels for the treatment of children with leukemia. Dr. Mittelman explained that these studies could eventually lead to improved treatment of children and adults with leukemia and lymphoma.