Study shows fasting kills cancer cells of common childhood leukemia

December 12, 2016
Dr. Jingjing Xie, Dr. Chengcheng "Alec" Zhang, and Dr. Zhigang Lu. Credit: UT Southwestern Medical Center

UT Southwestern Medical Center researchers have found that intermittent fasting inhibits the development and progression of the most common type of childhood leukemia.

This strategy was not effective, however, in another type of blood cancer that commonly strikes adults.

"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," said Dr. Chengcheng "Alec" Zhang, Associate Professor of Physiology at UT Southwestern and senior author of the study, published online today by Nature Medicine. "We also identified a mechanism responsible for the differing response to the fasting treatment," he added.

The researchers found that fasting both inhibits the initiation and reverses the progression of two subtypes of acute lymphoblastic leukemia, or ALL - B-cell ALL and T-cell ALL. The same method did not work with acute myeloid leukemia (AML), the type that is more common in adults.

ALL, the most common type of leukemia found in children, can occur at any age. Current ALL treatments are effective about 90 percent of the time in children, but far less often in adults, said Dr. Zhang, who also holds the Hortense L. and Morton H. Sanger Professorship in Oncology and is a Michael L. Rosenberg Scholar in Medical Research.

The two types of leukemia arise from different bone marrow-derived blood , he explained. ALL affects B cells and T cells, two types of the immune system's disease-fighting white blood cells. AML targets other types of such as macrophages and granulocytes, among other cells.

In both ALL and AML, the remain immature yet proliferate uncontrollably. Those cells fail to work well and displace healthy blood cells, leading to anemia and infection. They may also infiltrate into tissues and thus cause problems.

The researchers created several mouse models of acute leukemia and tried various dietary restriction plans. They used green or yellow florescent proteins to mark the cancer cells so they could trace them and determine if their levels rose or fell in response to the fasting treatment, Dr. Zhang explained.

"Strikingly, we found that in models of ALL, a regimen consisting of six cycles of one day of fasting followed by one day of feeding completely inhibited cancer development," he said. At the end of seven weeks, the fasted mice had virtually no detectible cancerous cells compared to an average of nearly 68 percent of cells found to be cancerous in the test areas of the non-fasted mice.

Compared to mice that ate normally, the rodents on alternate-day fasting had dramatic reductions in the percentage of cancerous cells in the bone marrow and the spleen as well as reduced numbers of white , he said. The spleen filters blood.

"In addition, following the fasting treatment, the spleens and lymph nodes in the fasted ALL model mice were similar in size to those in normal mice. Although initially cancerous, the few fluorescent cells that remained in the fasted mice after seven weeks appeared to behave like normal cells," he said. "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."

Fasting is known to reduce the level of leptin, a cell signaling molecule created by fat tissue. In addition, previous studies have shown weakened activity by leptin receptors in human patients with ALL. For those reasons, the researchers studied both and leptin receptors in the mouse models.

They found that mice with ALL showed reduced leptin receptor activity that then increased with intermittent fasting, he said.

"We found that fasting decreased the levels of leptin circulating in the bloodstream as well as decreased the leptin levels in the bone marrow. These effects became more pronounced with repeated cycles of fasting. 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," he added.

Interestingly, AML was associated with higher levels of leptin receptors that were unaffected by fasting, which could help explain why the fasting treatment was ineffective against that form of leukemia. It also suggests a mechanism - the pathway - by which fasting exerts its effects in ALL, he said.

"It will be important to determine whether ALL cells can become resistant to the effects of fasting," he said. "It also will be interesting to investigate whether we can find alternative ways that mimic fasting to block ALL development."

Given that the study did not involve drug treatments, just , researchers are discussing with clinicians whether the tested regimen might be able to move forward quickly to human clinical trials

Explore further: Simple compound could provide first new therapy for myeloid leukemia in four decades

More information: Nature Medicine , DOI: 10.1038/nm.4252

Related Stories

Simple compound could provide first new therapy for myeloid leukemia in four decades

September 16, 2016
Researchers at Massachusetts General Hospital (MGH) and the Harvard Stem Cell Institute (HSCI) have identified a drug compound that arrests in mice the progression of acute myeloid leukemia (AML), a bone marrow cancer that ...

Study determines efficacy of two drugs to treat a form of leukemia

October 24, 2016
Researchers have determined that two Phase 1 drugs (CX-4945 and JQ1) can work together to efficiently kill T-cell acute lymphoblastic leukemia cells while having minimal impact on normal blood cells.

Strategies to mimic fasting during chemotherapy enhance anticancer T cell activity in mice

July 11, 2016
Fasting is known to increase positive outcomes during cancer treatment, and now two independent studies in mice show that fasting, either through diet or drugs, during chemotherapy helps increase the presence of cancer-killing ...

Study provides new clues to leukemia resurgence after chemotherapy

June 2, 2016
For the first time, researchers have discovered that some leukemia cells harvest energy resources from normal cells during chemotherapy, helping the cancer cells not only to survive, but actually thrive, after treatment.

Scientists propose solution for blast cells' classification in diagnostics of acute lymphoblastic leukemia

September 19, 2016
Currently, diagnostics of acute leukemia are based on manual calculations of different types of cells by blood smears and bone marrow aspirations. The data from morphological research conducted by doctors in the microscopic ...

Fasting makes brain tumors more vulnerable to radiation therapy

September 11, 2012
A new study from USC researchers is the first to show that controlled fasting improves the effectiveness of radiation therapy in cancer treatments, extending life expectancy in mice with aggressive brain tumors.

Recommended for you

Shooting the achilles heel of nervous system cancers

July 20, 2017
Virtually all cancer treatments used today also damage normal cells, causing the toxic side effects associated with cancer treatment. A cooperative research team led by researchers at Dartmouth's Norris Cotton Cancer Center ...

Molecular changes with age in normal breast tissue are linked to cancer-related changes

July 20, 2017
Several known factors are associated with a higher risk of breast cancer including increasing age, being overweight after menopause, alcohol intake, and family history. However, the underlying biologic mechanisms through ...

Immune-cell numbers predict response to combination immunotherapy in melanoma

July 20, 2017
Whether a melanoma patient will better respond to a single immunotherapy drug or two in combination depends on the abundance of certain white blood cells within their tumors, according to a new study conducted by UC San Francisco ...

Discovery could lead to better results for patients undergoing radiation

July 19, 2017
More than half of cancer patients undergo radiotherapy, in which high doses of radiation are aimed at diseased tissue to kill cancer cells. But due to a phenomenon known as radiation-induced bystander effect (RIBE), in which ...

Definitive genomic study reveals alterations driving most medulloblastoma brain tumors

July 19, 2017
The most comprehensive analysis yet of medulloblastoma has identified genomic changes responsible for more than 75 percent of the brain tumors, including two new suspected cancer genes that were found exclusively in the least ...

Novel CRISPR-Cas9 screening enables discovery of new targets to aid cancer immunotherapy

July 19, 2017
A novel screening method developed by a team at Dana-Farber/Boston Children's Cancer and Blood Disorders Center—using CRISPR-Cas9 genome editing technology to test the function of thousands of tumor genes in mice—has ...

1 comment

Adjust slider to filter visible comments by rank

Display comments: newest first

Anonym
not rated yet Dec 13, 2016
....headline left out "in mice"

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.