In a study reported in the current issue of Cancer Research, Steven Mittelman, MD, PhD, and colleagues at The Saban Research Institute of Children’s Hospital Los Angeles report that obesity substantially impairs the ability of a first-line chemotherapy to kill leukemia cells.  Not only can obesity cause cancer; this research indicates how it can significantly decrease a child’s odds of battling the disease if they get it.

“This research really shines a light on how cancer cells avoid chemotherapy,” said Brent Polk, MD, director of The Saban Research Institute.  “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 one’s risk of dying from cancer. However, researchers at Children’s Hospital were the first to show that this effect may also be present in children: Obese children diagnosed with high-risk acute lymphoblastic leukemia (ALL) have a 50% greater risk of their disease recurring compared with children who are not obese.  This new study shows that obesity may impair the activity of L-asparaginase (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 ALL 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 ALL cells.

How Body Weight Impacts Cancer

These findings by Mittelman and colleagues are the latest installment of a frightening public health story.  In previous research using preclinical models, Mittelman has demonstrated that there are several ways in which obesity affects leukemia.  These include:

* Obesity directly accelerates 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

According to Mittelman, who is also an associate professor at the Keck School of Medicine of the University of Southern California, the increased incidence and worse prognosis experienced by obese individuals with cancer translates into more than a 50% increased risk of dying from cancer compared to 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.

“Our immediate goal is to develop strategies to counteract these effects of fat cells and obesity,” said Ehsan Ehsanipour, who is a master’s student in the Mittelman lab, and first author on the Cancer Research paper.  “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.

This work was financially supported by the Gabrielle’s Angel Foundation, the NIH/NCI and the NIH NCRR CTSI.

About Children’s Hospital Los Angeles

Children’s Hospital Los Angeles has been named the best children’s hospital in California and among the top five in the nation for clinical excellence with its selection to the prestigious US News & World Report Honor Roll.  Children’s Hospital is home to The Saban Research Institute, one of the largest and most productive pediatric research facilities in the United States, is one of America’s premier teaching hospitals and has been affiliated with the Keck School of Medicine of the University of Southern California since 1932.

For more information, visit www.CHLA.org.