Obese lab mouse
Switching to a low-fat diet can improve survival in obese mice with acute lymphoblastic leukemia (ALL), according to new research.
Diet-induced obese (DIO) mice with ALL had a survival rate of 17% if they remained on a high-fat diet while treated with vincristine, but survival rose to 92% for mice that were switched to a low-fat diet before treatment.
However, the dietary switch did not impact the survival of DIO mice treated with dexamethasone or L-asparaginase monotherapy.
Researchers reported these findings in Cancer & Metabolism.
“The most exciting thing, to me, about this study is the fact that this shows that a dietary intervention could potentially help us kill leukemia cells in children with acute lymphoblastic leukemia,” said study author Steven Mittelman, MD, PhD, of the University of Southern California, Los Angeles.
“The current treatments for leukemia are very toxic, so finding a way to use a healthy diet, without increasing the toxicity of therapy to treat people with cancer, would be incredible.”
Building on previous research that showed obesity reduced the effectiveness of chemotherapeutic drugs in children with leukemia, the researchers tested whether a dietary intervention could improve ALL outcomes in obese mice.
Methods
The team used NOD/SCID IL2-receptor gamma chain knockout mice raised on either a 60% or 10% fat-calorie diet. Only male mice were studied because female mice do not become as significantly obese on the high-fat diet.
The researchers implanted GFP+ pre-B-cell ALL transgenic mouse cells into DIO and control mice at about 20 weeks old.
Six to seven days after ALL implantation, the researchers randomized the DIO mice to continue their high-fat diet or switch to the control diet (10% calories from fat).
In some experiments, mice received monotherapy with vincristine, and other experiments used L-asparaginase or dexamethasone.
In additional experiments, the researchers implanted DIO and control mice with patient-derived ALL cells with normal karyotype.
After 17 days of engraftment, the researchers switched half the DIO mice to the control diet. The next day, they treated these mice with vincristine, L-asparaginase, or dexamethasone for 4 weeks.
The team monitored the mice daily for food intake, body weight, and onset of progressive leukemia.
Results
Diet had no impact on DIO or control mice that did not receive chemotherapy. Time to progression was the same in these mice.
When vincristine was started on day 7 after ALL implantation, DIO mice switched to the low-fat diet had the best survival, even better than the control mice.
Overall survival was 92% for the DIO mice that switched diets, 42% for the control group, and 17% for the DIO group maintained on the high-fat diet.
Survival experiments performed using L-asparaginase or dexamethasone monotherapy showed no impact of switching diets. The researchers reported there was “no detectable effect on survival in these experiments.”
The team believes this is the first study to test a diet intervention on treatment outcome in hematologic malignancy.
The researchers plan to study dietary intervention further in both obese and non-obese patients.
This study was supported by the National Cancer Institute and funds from the Saban Research Institute, Children’s Hospital of Los Angeles. The researchers had no competing interests to declare.