Researchers have discovered a new target for leukemia treatment after their study revealed that cancerous cells utilize vitamin B-6. The development of a new drug that could prove to be more effective than current treatments is underway. Leukemia — a form of blood cancer that typically affects children and older adults — is the 10th most common cancer in the United States, representing 3.5% of all new cancer cases in the country. According to the National Cancer Institute, the disease is also the fifth highest cause of U.S. cancer deaths. Figures show an estimated 22,840 people died as a result of leukemia in 2019. Acute myeloid leukemia (AML) is the second most common form of the disease. AML spreads quickly, leading to a comparatively low survival rate. Less than one-third of people with AML survive for 5 years after being diagnosed. AML’s cancerous cells divide faster than the current treatment can kill them. Finding a new therapy that better targets these cells is crucial for long-term survival. Cancer cells use metabolism changes — where chemical reactions result in various cell functions being switched on or sped up — to grow and spread at an abnormal rate. As Lingbo Zhang, a fellow at the Cold Spring Harbor Laboratory (CSHL), NY, explains in a video: “One central feature of [a] leukemic cell is that its metabolic processes have been reprogrammed to support abnormal cell growth.” A vitamin’s role Zhang and a team from both CSHL and Memorial Sloan Kettering Cancer Center (MSK), NY, have now discovered how AML cell division happens so speedily. Surprisingly, it revolves around a particular vitamin. Vitamin B-6 is essential for the body to function normally. Derived solely from a person’s diet, it helps with cell growth and metabolism, as well as producing neurotransmitters and red blood cells. Taking genes from AML’s cancerous white blood cells, Zhang studied them to find more than 230 separate genes that were “very active in leukemic cells.” The team tested each one using CRISPR gene-editing technology to block the activity of each gene. The authors published their findings in the Cancer Cell journal. Used and abused by cancer The scientists aimed to find a gene that halted the spread of the cancerous cells, and they did: a gene that produces a metabolic enzyme called pyridoxal kinase (PDXK). PDXK controls the usage of vitamin B-6 by making proteins that, in turn, produce the active form of the vitamin. When cells are healthy, they do not need vitamin B-6 all the time. The enzyme activates it when the time is right for cells to divide. However, the researchers found that in rapidly dividing cancerous cells, the enzyme promoted this vitamin. This led to the proliferation of the AML cells, which could potentially lead to further growth and spread of the disease. “We have shown that this enzyme is essential for leukemic cell growth,” Zhang says, explaining: “Leukemic cells are addicted to vitamin B-6. You can call it a vulnerability of the cancer.” Scott Lowe, co-author and chair of the Cancer Biology and Genetics Program at MSK, adds: “We already knew that vitamin B-6 served as a regulator for a whole series of enzymes that are needed to make the building blocks required for cell growth and proliferation.” But, he says, “this research suggested for the first time that the vitamin B-6 pathway might be important for sustaining cancer.” The path to a more effective treatment Most importantly, this enzyme and vitamin combination could be a target for a new, more effective form of therapy. It would not be as simple as reducing patients’ vitamin B-6 intake because this may affect vital functions throughout the body, including the brain and the rest of the central nervous system. Instead, Zhang and his colleagues are working with medicinal chemists to develop a drug that influences the PDXK enzyme. By doing this, leukemic cells would not be able to use vitamin B-6 to their advantage. The method might not only slow or halt the spread of leukemia, but it could also avoid harming healthy cells that require vitamin B-6 for survival. “We hope we can develop a potential therapeutic strategy for this lethal disease,” says Zhang. Source
