Doctors at Los Angeles' Children's Hospital have discovered a link between obesity and a significant decrease in a child's ability to fight leukemia, according to a recently released research study.
In a study -- outlined in the current issue of Cancer Research -- physicians and researchers at the hospital's Saban Research Institute report that obesity substantially impairs the ability of a first-line chemotherapy to kill leukemia cells.
Fat cells have a large amount of an enzyme that help produce glutamine, which has the potential to feed nearby leukemia cells and help them fight chemotherapy.
"This research really shines a light on how cancer cells avoid chemotherapy," Saban Research Institute Director Dr. Brent Polk said. "As childhood obesity has become a global challenge, our understanding of how to beat cancer in children is advanced by these important findings."
Obesity is known to greatly increase adults' risk of dying from cancer.
However, researchers at Children's Hospital were the first to show that this effect also may be present in children.
Obese children diagnosed with high-risk acute lymphoblastic leukemia have a 50 percent greater risk of their disease recurring compared with children who are not obese.
The new study shows that obesity may impair the activity of ASNase, a first-line choice of chemotherapy drugs for treating this disease.
ASNase acts by breaking down the amino acids asparagine and glutamine, building blocks that the leukemia cells need to survive and proliferate.
The investigators found that fat cells produce these amino acids, and so decrease the ability of ASNase to eradicate the cells.
The findings are the latest installment of a frightening public health story.
In previous Children's Hospital research, it has been demonstrated that there are several ways in which obesity can accelerate the progression of leukemia.
- Some chemotherapies accumulate in fat tissue, making less drug available to destroy leukemia cells
- Fat cells attract leukemia cells to areas like the bone marrow and fat tissue, where they are harder to treat with chemotherapy
- Fat cells protect leukemia cells from a variety of chemotherapies likely through secretion of survival molecules
The Saban institute's Dr. Steven Mittelman said the increased incidence and worse prognosis experienced by obese individuals with cancer translates into more than a 50 percent increased risk of dying from cancer compared with their lean counterparts.
Given that leukemia is the most common cancer in children and that the incidence of childhood obesity has reached epidemic proportions, there is an urgent need to intervene and prevent a potential increase in the number of children dying from leukemia, according to Mittelman.
Mittelman's sense of urgency is echoed by his colleague Ehsan Ehsanipour, a master's student and first author of the research study.
"Our immediate goal is to develop strategies to counteract these effects of fat cells and obesity," Ehsanipour said. "For example, forms of ASNase which break down glutamine faster might have a better effect in obese children."
Other projected clinical studies include testing whether diet or exercise could help the prognosis of obese pediatric patients with leukemia.