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Source: Thailand Medical News  Jan 14, 2020  7 months ago
Researchers Discover Vitamin B6 Accelerates Acute Myeloid Leukemia Progression
Researchers Discover Vitamin B6 Accelerates Acute Myeloid Leukemia Progression
Source: Thailand Medical News  Jan 14, 2020  7 months 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
 

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Source : Thailand Medical news
Feb 05, 2020  6 months ago