Vitamin C against leukemia

Ascorbic acid prevents blood stem cells from becoming a breeding ground for leukemia

Kirill Stasevich, "Science and Life"

Leukemia occurs due to damaged blood stem cells that stop developing - they no longer produce mature erythrocytes, lymphocytes, leukocytes, instead, immature progenitor cells accumulate in the blood, which can't do anything else but divide. 

In turn, stem cells stop developing due to mutations, and some of the most famous leukemic mutations are those that disable the TET2 gene. It encodes an enzyme that regulates the activity of many other genes, in particular, the TET2 protein turns on the genes necessary for the differentiation of stem cells at the right moment. 

It is clear that if it does not work, then the cells remain in an intermediate state, unable to acquire specialization. Usually mutations in TET2 are encountered in the case of acute myeloid leukemia and myelodysplastic syndrome. 

Researchers from New York University, who studied the role of the TET2 gene in the development of leukemia, modified mouse TET2 so that it could be turned on and off at will. Bone marrow cells with modified TET2 were then transplanted into normal, healthy mice, with which no modifying procedures were performed – and healthy animals soon showed signs of leukemia. But if TET2 was turned on, then the symptoms of the disease weakened, the disease did not develop further. 

That is, if the mutated gene is made to work, leukemia can be defeated. But how to do it? In fact, a damaged gene can be left alone, because in the genome it is in two copies: on the chromosome inherited from the father, and on the chromosome inherited from the mother. In most patients with leukemia, only one of the copies is damaged. And all you need is to find a way to increase the activity of the second, healthy copy of TET2, so that it works both for itself and for the mutant copy. 

Such a remedy, as the researchers write in an article in Cell, turned out to be vitamin C, or ascorbic acid. Recall that the TET2 enzyme regulates the activity of genes – it removes certain chemical labels from DNA, after which the genes become available for reading information. In order for TET2 to work, it needs iron, and in a certain form. And in order for iron to acquire this most convenient form for TET2, vitamin C is needed.

Experiments with human leukemic cells have shown that vitamin C enhances the activity of the TET2 enzyme, and that in the presence of vitamin C, such changes occur in the DNA structure that open the way to cellular differentiation. 

Ascorbic acid inhibited the development of the disease in mice with transplanted leukemic cells – stem cells with stimulated TET2 did not stop developing, but turned into ordinary blood cells. 

Finally, when mice were no longer transplanted with mouse, but with human diseased cells (the animals had previously specifically lowered the activity of the immune system so that it would not attack foreign material), then in this case vitamin C was able to stop the development of a malignant disease. (It is worth noting here that the doses of ascorbic acid necessary for therapeutic action turned out to be quite high, and no matter how much we, for example, ate oranges and lemons, etc., it would not be possible to achieve the desired concentration of vitamin in the blood through food.) 

If we talk about clinical prospects, ascorbic acid, obviously, will be very useful when the patient cannot withstand conventional chemotherapy or bone marrow transplantation. In the near future, the authors of the work are going to conduct experiments with real cases of leukemia – and at the same time find out what other types of blood cancer vitamin C can work against. Perhaps, given the mechanism of its antileukemic effect, it will be possible to develop other molecules that will work the same way, but more effectively. 

Portal "Eternal youth" http://vechnayamolodost.ru  30.08.2017