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Vitamin C slows leukaemia in mice by tweaking key gene

21 August 2017
Appeared in BioNews 914

High doses of vitamin C may help fight certain leukaemias by boosting the activity of a particular gene, suggests a new study.

Daily injections of vitamin C slowed the progression of leukaemia in mice with a faulty gene called TET2, and increased efficacy of drug treatment.

'We're excited by the prospect that high-dose vitamin C might become a safe treatment for blood diseases caused by TET2-deficient leukaemia stem cells, most likely in combination with other targeted therapies,' said corresponding study author Professor Benjamin Neel, at the Perlmutter Cancer Centre, New York University (NYU) Langone Health.

In leukaemia, cancerous cells often have mutations in gene called TET2 - its activity normally encourages blood stem cells to develop into mature white blood cells, which eventually die. Without TET2, the stem cells can multiply uncontrollably leading to leukaemia.

In the study, published in the journal Cell, the scientists genetically engineered mice such that they could reversibly lower TET2 expression, mimicking the low levels seen in patients. When researchers lowered TET2, the stem cells malfunctioned and the mice began to develop cancer. When they turned levels back up, disease progression halted.

Most patients with TET2 mutations do not have a complete loss of the protein, because they only have a mutation in one copy of the gene, first author Dr Luisa Cimmino of NYU Langone Health told The Scientist. 'And if we could only bring [its] activity back to normal levels, it would be like restoring the protein back to normal levels. That's where the vitamin C comes in.'

The team found that daily vitamin C - previously shown to stimulate the activity of TET2 - slowed the progression of leukaemia, inducing the faulty stem cells to mature and later die. In effect, giving the vitamin mimicked the effect of restoring TET2 genetically.

The researchers also found that vitamin C enhanced the sensitivity of leukaemia stem cells to a type of cancer drug, PARP inhibitors, in vitro. These drug types are known to cause cancer cell death by blocking the repair of mutations damage, and are already approved for treating certain patients with ovarian cancer, said Dr Cimmino.

'If these findings withstand clinical testing, the impact for patients with blood cancers could be significant,' Dr Eirini Papapetrou of the Icahn School of Medicine at Mount Sinai in New York City told The Scientist.

Professor Neel cautioned against eating excessive amounts of vitamin C, as humans can only get the levels required intravenously. He also added that while there are some health benefits to vitamin C, 'they're unlikely to be a general anti-cancer therapy'.

His team is moving forward with clinical trials to test the efficacy of vitamin C combined with other therapies in certain leukaemias.

Restoration of TET2 function blocks aberrant self-renewal and leukemia progression
Cell |  17 August 2017
Vitamin C Blocks Leukemia Progression in Mice
The Scientist |  17 August 2017
Vitamin C helps genes to kill off cells that would cause cancer
New Scientist |  17 August 2017
Vitamin C may encourage blood cancer stem cells to die
EurekAlert |  17 August 2017
Vitamin C may stop leukemia from progressing
Medical News Today |  17 August 2017
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