According to a new study, the amino acid valine, which serves as a molecular building block for many animal proteins, plays a critical role in the cancerous growth seen in T cell acute lymphoblastic leukemia (ALL).
The findings of the study were published in the ‘Nature Journal’.
The study, which was conducted by researchers at NYU Langone Health, its Department of Pathology, and the Laura and Isaac Perlmutter Cancer Center, discovered that genes involved in the use of valine in cells were more active in cancerous T cells than in normal T cells. The findings were published in the journal Cancer Cell.
The inhibition of these valine-linked genes not only resulted in a decrease in valine in leukaemia blood T cells, but it also prevented the growth of tumour cells in the laboratory. Only 2% of cancerous T cells were still alive after being removed from the body.
Experiments have also suggested that changes (mutations) in the DNA code of the NOTCH1 gene, which is the most commonly found in patients who develop leukaemia, may promote cancer growth in part by increasing valine levels in the blood.
The research involved experiments with human leukaemia cells that were grown in the lab and then transplanted into mice that developed this cancer, which has its origins in white blood cells in the bone marrow, as a result of the transplantation.
Experiments carried out in the laboratory revealed that feeding the leukemic mice low-valine diets for three weeks stopped the growth of tumors. In addition, the diet reduced the number of cancer cells in the blood by at least half, and in some cases to undetectable levels. The reintroduction of valine into the diet, on the other hand, resulted in the progression of cancer.
“Our study confirms that T cell acute lymphoblastic leukaemia is completely dependent on a supply of valine, and that a deficiency in valine can prevent the progression of this cancer,” said Palaniraja Thandapani, PhD, a postdoctoral fellow at New York University Grossman School of Medicine and the Perlmutter Cancer Center, who was not involved in the study.
The research team intends to test whether diets low in valine-rich foods, such as meat, fish, and beans, are an effective treatment for cancer patients the following year, if the results are positive. Because they are already being used to treat acid imbalances in the body associated with genetic disorders that affect gut metabolism, Thandapani explained, low-valine diets are readily available, he added.
Iannis Aifantis, PhD, a senior study investigator, stated that the trial design would most likely combine diet therapy with venetoclax, a drug that is already approved for use in the United States for the treatment of most other types of leukemia.
According to him, the drug combination is critical because such dietary restrictions are unlikely to be sustainable over the long term in most cases. This is due to the well-documented dangers of muscle wasting and brain damage associated with long-term valine deficiency.
Dr. Aifantis is the Hermann M. Biggs Professor and chair of the Department of Pathology at NYU Grossman and Perlmutter. “Our clinical approach would involve using low-valine diets to shrink the number of T cells in acute lymphoblastic leukemia to a level so low that drugs could then effectively stall cancer progression,” he explained.
Cancer growth and spread, according to Aifantis, necessitate the presence of numerous fundamental cell building blocks, such as proteins, nucleotides, and fatty acids. At least a half-dozen other amino acids, particularly high levels of lysine, have been implicated in cancer, but the precise nature of their contributions is still unclear. He expressed concern that dietary strategies for cancer treatment have been tried for decades with little scientific evidence of any benefit. His team’s planned clinical trial is just one example of the additional research that will be needed before any treatment guidelines can be recommended.
According to the American Cancer Society, more than 1,500 people in the United States die each year from T cell acute lymphoblastic leukemia, the majority of whom are children. Another 5,000 people will be diagnosed for the first time. This type of cancer is responsible for approximately one-quarter of all leukaemia cases.
National Institutes of Health grants P30CA016087, P01 CA229086, and R01 CA228135, as well as the Leukemia & Lymphoma Society, the New York State Department of Health’s Study finds nutrient’s role in childhood blood cancerNYSTEM program, and the American Association for Cancer Research Incyte Corporation Leukemia Research Fellowship provided support for the study.
Thandapani, Aifantis, and Tsirigos were joined by co-lead investigators Andreas Kloetgen, Matthew Witkowski, and Christina Glytsou, as well as study co-investigators Anna Lee, Eric Wang, Jingjing Wang; Sarah LeBoeuf; Kleopatra Avrampou; and Thales Papagiannakopoulos, all of whom worked at NYU Langone.