A team of researchers from California and Japan has found that an essential amino acid plays a crucial role in the creation of blood stem cells—a discovery the scientists say could offer a potential alternative to chemotherapy and radiation in treating blood cancer patients.
The amino acid valine, which people obtain by eating protein, appears key to the formation of blood stem cells. Mice deprived of the protein building block for two to four weeks stopped making new blood cells altogether, according to the new study, published Thursday in Science.
In lab tests the study showed human blood stem cells also appear to be as dependent on valine, the researchers said. If this proves true, depriving patients of the amino acid before a bone marrow transplant might spare them the necessity of chemotherapy or radiation, both of which destroy blood stem cells to make room for new, transplanted ones. But with these procedures one in 20 transplant patients dies, sometimes from complications linked to the toxic treatments.
Additionally, depriving certain leukemia patients of valine might even kill off the cells that are causing their cancers, says Hiromitsu Nakauchi, a senior author on the new paper. “If such a simple and relatively less harmful therapy could be used to treat leukemias, that would be great,” says Nakauchi, a stem cell researcher at both the University of Tokyo and Stanford University. “That’s what I’m hoping at the moment.” Nakauchi adds that he was surprised to uncover such a basic biological process. “I couldn’t believe it myself,” he says.
Camilla Forsberg, a blood stem cell researcher at the University of California, Santa Cruz, who was not involved in the research, says she was impressed with the results and thrilled there are still such fundamental discoveries to be made. “It’s pretty exciting how the basic things we think about are still giving us surprises,” she says, adding that it will be crucial to figure out why these blood stem cells—also called hematopoietic cells—are so sensitive to valine. Other cell types might have particular sensitivities to the other 19 amino acids active in the body, nine of which are vital and must be obtained via food, so Forsberg believes these must now be studied as well. The essential role valine plays in blood should not come as such a surprise, says Linheng Li, a stem cell biologist at the Stowers Institute for Medical Research. Some people who eat a low-protein vegetarian diet are known to develop anemia, a disease characterized by low levels of red blood cells.
Li was not involved in the new research, but says he made a similar, unpublished finding in his own lab that makes him confident of Nakauchi’s results. He also thinks valine deprivation could work as well in people as it does in mice, although it will take a lot of research to determine how long people can tolerate being deprived of the amino acid. If valine deprivation works in bone marrow transplant patients, it could open the procedure to some people—such as pregnant women—who are usually not considered candidates for chemotherapy or radiation, he says. Li suspects, however, that valine deprivation alone will not be effective for treating cancer directly, although it might work well combined with other therapies.
In the new study Nakauchi and his colleagues say they were able to successfully transplant bone marrow in valine-deprived mice without needing radiation or chemotherapy—but some of the mice died from lack of the nutrient, which is also involved in metabolism and tissue repair. Nakauchi says it should be relatively easy to deprive people of valine by feeding them on specially formulated intravenous diets, although he admits that might be difficult if the depletion needs to last weeks or months.
The researchers also found human blood stem cells failed to proliferate when cultured without valine. Nakauchi says the team realized only after their study was completed that it built on research published 70 years ago in Science by the late Nobel laureate Arthur Kornberg. When Nakauchi was a postdoctoral student at Stanford he knew the biochemist, and says it made him proud to renew and extend Kornberg’s findings.
Now Nakauchi says he hopes the work will lead to new approaches to cancer treatment. “There may be some other, similar amino acid–dependency in other stem cells and also cancer stem cells,” he says. “Those are the things I’m very much interested in.”