There are two types of ALL: B cell ALL, which begins in the B lymphocytes (B cells), and T cell ALL, which begins in the T lymphocytes (T cells).
ALL stops B cells and T cells from maturing. As a result, large numbers of immature, leukemic cells are released into the bloodstream, outweighing the number of healthy white blood cells, red blood cells, and platelets.
The reduction in healthy white blood cells makes a patient vulnerable to infection, while low levels of platelets and red blood cells can lead to unusual bleeding and anemia. Other signs and symptoms of ALL include fatigue, loss of appetite, fever, rib pain, and bone or joint pain.
Chemotherapy is the primary treatment for children with ALL, and more than 95 percent of children achieve remission after 1 month of induction chemotherapy - that is, they show no signs of leukemia in bone marrow samples after an intense chemotherapy drug regimen.
However, this does not always mean the cancer has gone for good; the disease returns for around 15-20 percent of children who are treated for ALL.
In the new study, senior author Dr. Chengcheng Zhang, associate professor of physiology at the University of Texas Southwestern (UT Southwestern) Medical Center, and colleagues suggest fasting could be a feasible treatment for childhood ALL.
Intermittent fasting cleared cancer cells, increased survival of ALL mice
The researchers note that previous studies have suggested fasting can boost the anti-cancer effects of chemotherapy. However, the underlying mechanisms for this association have been unclear.
For their study, Dr. Zhang and colleagues set out to gain a better understanding of how fasting affects cancer cells in several mouse models of ALL.
The mice were subject to either dietary restriction or normal feeding. To monitor cancer cell response to each dietary pattern, the researchers "marked" the rodents' cancer cells with green or yellow fluorescent proteins.
The researchers identified one dietary restriction regimen that appeared to kill leukemia cells and halt development of both ALL subtypes.
"Strikingly, we found that in models of ALL, a regimen consisting of six cycles of 1 day of fasting followed by 1 day of feeding completely inhibited cancer development," explains Dr. Zhang.
After 7 weeks, the researchers found that the mice that followed the fasting regimen had almost no detectable leukemia cells in bone marrow and the spleen - the organ that filters blood - while around 68 percent of cells were found to be cancerous in non-fasting mice.
"Although initially cancerous, the few fluorescent cells that remained in the fasted mice after 7 weeks appeared to behave like normal cells. Mice in the ALL model group that ate normally died within 59 days, while 75 percent of the fasted mice survived more than 120 days without signs of leukemia."
Dr. Chengcheng Zhang
What is more, the team found that the spleens and lymph nodes of mice that were subject to intermittent fasting were comparable in size to those of normal mice.
The researchers also tested the effects of fasting on mouse models of acute myeloid leukemia (AML) - a form of leukemia that is more common in adults - but they found it had no effect.
Fasting increases leptin receptor activity
According to the researchers, fasting reduces levels of a hormone called leptin - known as the "satiety hormone" because it regulates appetite. Previous studies have shown that in patients with ALL, leptin receptor activity is decreased.
With this in mind, Dr. Zhang and team decided to monitor leptin levels and leptin receptor activity in the mouse models.
As expected, the researchers identified reduced leptin receptor activity in mice with ALL. However, they found that this activity increased in the mice subject to intermittent fasting.
"We found that fasting decreased the levels of leptin circulating in the bloodstream as well as decreased the leptin levels in the bone marrow," explains Dr. Zhang.
"These effects became more pronounced with repeated cycles of fasting," he adds. "After fasting, the rate at which the leptin levels recovered seemed to correspond to the rate at which the cancerous ALL cells were cleared from the blood."
The researchers point out that mouse models of AML already had higher leptin receptor activity, and this activity was not affected by intermitted fasting. This, they say, might explain why fasting has no effect on this type of leukemia.
Overall, the authors believe their research suggests a possible pathway by which fasting might prevent the development and progression of ALL.
"This study using mouse models indicates that the effects of fasting on blood cancers are type-dependent and provides a platform for identifying new targets for leukemia treatments. We also identified a mechanism responsible for the differing response to the fasting treatment."
Dr. Chengcheng Zhang
In future research, the team plans to search for fasting-mimicking strategies that can halt ALL development.
Because the study only tested fasting - not drugs - the researchers believe it is possible that progression to human clinical trials may be quicker.
Fasting selectively blocks development of acute lymphoblastic leukemia via leptin-receptor upregulation, Chengcheng Zhang et al., Nature Medicine, doi:10.1038/nm.4252, published online 12 December 2016.
UT Southwestern Medical Center news release, accessed 13 December 2016 via EurekAlert.
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Dana-Farber/Boston Children's Cancer and Blood Disorders Center, Relapsed acute lymphoblastic leukemia (ALL), accessed 13 December 2016.
National Cancer Institute, General information about childhood acute lymphoblastic leukemia, accessed 13 December 2016.