Source: Thailand Medical News Jan 14, 2020 4 years, 11 months, 1 week, 4 days, 6 hours, 29 minutes ago
Medical scientists have discovered that
Acute Myeloid Leukemia (
AML) grows by taking advantage of the
vitamin B6 to accelerate cell division. The research team from Cold Spring Harbor Laboratory (CSHL) and Memorial Sloan Kettering Cancer Center (MSK) suggest they could halt the growth of this
cancer by limiting its ability to manipulate the enzyme that pushes
vitamin B6 to make proteins essential for cell division. It's an approach to attacking
cancer without harming healthy cells, which need the
vitamin B6 to survive.
At the moment, only one-third of
Acute Myeloid Leukemia patients will survive five years after diagnosis. That's because, like many other deadly
cancers, the cells involved in this aggressive form of blood
cancer can divide and spread faster than most treatments can kill them.
Dr Lingbo Zhang, a CSHL Fellow wanted to know how
Acute Myeloid Leukemia can achieve such rapid growth, so he looked closely at the genes of the disease's cancerous white blood cells.
D Zhang told
Thailand Medical News, "We found more than 230 genes that are very active in leukemic cells and then we tested them, one by one.”
Utilizing CRISPR gene-editing technology, Zhang's lab shut down the activity of each of these 230 suspect genes to see if their absence would stop the
cancer cells from proliferating. Among the hundreds of genes they tested, one pattern emerged. The gene which produces PDXK, the enzyme that helps cells use
vitamin B6, proved most important for the growth of the
cancer.
Dr Scott Lowe, a former CSHL fellow and currently the chair of the
Cancer Biology and Genetics program at MSK, said "while the action of certain vitamins has previously been linked to cancer, the specific links between
vitamin B6 identified here were unexpected."
Typically,
B6 vitamin is crucial to cell metabolism, producing energy and other resources important for cell growth. In a healthy cell, the PDXK enzyme manages the activity of
vitamin B6, making sure that the
vitamin does the job when needed. Because normal cells don't actually divide all the time, the PDXK enzyme isn't always pushing the
B6 vitamin to be active.
However, It's a different dynamic in
cancer cells, w
hich divide more frequently than normal cells. In
Acute Myeloid Leukemia cells, Zhang saw that the PDXK enzyme was always pushing
vitamin B6 activity. What this shows is that, "leukemic cells are addicted to
vitamin B6," he said. "You can call it a vulnerability of the
cancer."
Dr Zhang cautions that his research on how
cancer cells use the
B6 vitamin to proliferate does not mean that
cancer patients would necessarily benefit from reduced intake of
vitamin B6 as part of their diet. The
B6 vitamin is necessary for the survival of healthy cells. Zhang's research shows that
cancer cells take advantage of the PDXK enzyme to increase
B6 vitamin activity. This increased activity fuels
Acute Myeloid Leukemia growth.
Dr Zhang and his colleagues say the next step is to develop a drug that specifically blocks
leukemia from activating the PDXK enzyme. By manipulating the way the enzyme manages the activity of
vitamin B6, a drug could slow or even stop the growth of cancerous cells without the profound side effects that would result from completely eliminating
vitamin B6 from healthy cells. With the help of medicinal chemists, the team is now exploring this route.
Reference : Chen et al, Vitamin B6 addiction in acute myeloid leukemia, Cancer Cell, January 13, 2020. DOI: 10.1016/j.ccell.2019.12.002
