Monday August 21 2017

AML is an aggressive cancer of the white blood cells

"Super-strength vitamin C doses could be a way to fight leukaemia," the Mail Online reports. Research in mice found vitamin C could help combat the effect of a mutated gene that can cause uncontrollable stem cell growth and trigger the onset ofacute myeloid leukaemia (AML).

AML is an aggressive cancer of the white blood cells that usually affects older people. It is thought that some cases of AML are caused by a mutation in the Tet Methylcytosine Dixoygenase 2 (TET2) gene. This gene helps mature stem cells into specialised white blood cells. The mutation can lead to uncontrollable growth of cancerous cells leading to AML.

The researchers used mice to explore whether use of vitamin C could restore the TET2 gene to working order and help slow the progression of leukaemia.

The study found that using high doses of vitamin C intravenously did in fact suppress the growth of leukaemia cancer stem cells in the mice.

Although this does pave the way for future therapeutic approaches, this study was very early stage research in mice, and therefore would require further investigation and trials in humans before any treatment based on the findings could beoffered to patients.

Also, the dose used was far higher relative to weight, than would be safe in humans. It would be the equivalent of a human taking 300g of vitamin C,which would mean eating more than 5,000 oranges. So scientists would also have to find a way to lower the dose while achieving the same beneficial effect.

The study was carried out by researchers from several institutions, including New York University and Monash University in Australia. It was funded by numerous institutions such as the US NIH, the Leukaemia & Lymphoma Society and the Chemotherapy Foundation.

The study was published in thepeer-reviewed scientific journal Cell.

The UK media's coverage on this topic was generally accurate, highlighting that this is not a treatment that would be used by itself, but instead in combination with other approaches, such as chemotherapy.

This was an animal study which investigated whether treatment with vitamin C could restore function of Tet Methylcytosine Dixoygenase 2 (TET2) and therefore block the progression of leukaemia in mice.

TET2 is one of the most frequent mutations in diseases and cancers of the blood such as leukaemia. The TET2 gene encodes a protein involved in the production of bone marrow and blood cells. As a result, defects and mutations of TET2 can negatively affect the process which causes stem cells to turn into blood cells. In turn, this can promote the progression of leukaemia.

The researchers wanted to explore the role of TET2 deficiency in the maintenance of leukaemia stem cells.

The researchers further investigated whether vitamin C could be useful in the treatment of blood cancers. This is because treatment with vitamin C has previously been tested in solid tumours (tumours located in one part of the body, such as the lungs) and in some cases, been found to result in better patient outcomes.

Animal studies such as this are useful for early stage research. Butwhile there are many genetic similarities between mice and humans, we aren't identical. Therefore further testing is required in people to be sure of the effect of any treatment.

The researchers implanted leukaemia stem cells, extracted from humans, into mice and also used mice that were deficient in TET2.

To determine the effects of mutations that could reduce TET2 function, the mice were genetically engineered so that the TET2 gene could be switched on or off.

High doses of vitamin C were then administered intravenously to the mice and the function of TET2 and cell behaviour was studied.

The researchers also tested the use of vitamin C alongside PARP inhibitors. PARP inhibitors are a class of chemotherapy drugs that can help repair damaged DNA.

The researchers found that when the function of TET2 was switched off in the mice, abnormal stem cell behaviour occurred. This was reversed however once the function of TET2 was switched back on, confirming that loss of function of TET2 would in fact play a role in the formation of cancerous stem cells in diseases such as leukaemia.

In the TET2 deficient mice, the effects of TET2 deficiency were reversed following having intravenous vitamin C administered. The vitamin C treatment also induced the stem cells to mature and suppressed the growth of leukaemia cancer stem cells in the mice implanted with cell lines from human patients with leukaemia.

The researchers also found that following vitamin C treatment, the leukaemia cell lines were more sensitive to treatment with PARP inhibitors.

The researchers concluded: "We have found that targeted restoration of Tet2 is sufficient to block aberrant self-renewal of pre-leukemic stem cells. Similarly, vitamin C, by enhancing the activity of TET family dioxygenases, acts as a pharmacologic mimic of Tet2 restoration. Moreover, genetic or pharmacological restoration of TET activity confers an emergent vulnerability in leukemia cells, rendering them more sensitive to PARP inhibitors. Together, these results suggest new therapeutic strategies for clonal hematopoiesis, MDS and AML."

This mouse study explored whether treatment with vitamin C could restore function of TET2 and therefore block the progression of blood cancers like leukaemia.

It found that using high doses of vitamin C intravenously did in fact suppress the growth of leukaemia cancer stem cells in the mice implanted with cell lines from human patients with leukaemia.

It also reported that using vitamin C alongside existing treatment with PARP inhibitors helped reduce the progressions of the disease.

The researchers suggest that in the future, vitamin C could be used alongside chemotherapy and other conventional treatment forms.

This is exciting early stage research, with potential to pave the way for future treatment options for leukaemia and other blood cancers.

One of the challenges of treating acute myeloid leukaemia is that patients are usually older so it is often not safe to use very aggressive forms of chemotherapy. Hopefully vitamin C, or a similar substance, could help enhance the effects of milder forms of chemotherapy.

However, because this was an animal study, these results would need further investigation and have to undergo clinical trials in humans before new treatments based on these findings could be offered to patients.

It is far too soon to start taking high doses of vitamin C on the basis of this research, especially as large amounts of the vitamin (more than 1g per day per person) can cause stomach upsets. Some mice in this study received 100 milligrams, which would be equivalent to humans receiving 300g of pure vitamin C.

From what we know about AML, it would seem that the one way to reduce your chances of developing this cancer is to quit smoking.

See original here:
Vitamin C injections could play a role in treating blood cancers - NHS Choices