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Vitamin C regulates stem cell function and risk of leukaemia

by ecancer reporter Janet Fricker

Ascorbate (Vitamin C) regulates the function of stem cells and suppresses development of leukaemia, finds a study published in Nature.

In western countries, plasma ascorbate levels vary 10-fold among individuals, with men in the lowest quartile for plasma levels known to have significantly higher cancer mortality.

Furthermore, patients with haematological malignancies have significantly lower serum ascorbate than healthy controls.

Historically, stem cell metabolism has been difficult to study due to the large number of cells required for metabolic analysis.

In the current study, Michalis Agathocleous and investigators, from the Children’s Medical Center Research Institute at UT Southwestern (CRI), developed a ‘metabolomics’ technique combining rapid cell isolation by flow cytometry with liquid chromatography-mass spectrometry.

Using the technique, which allowed them to measure approximately 60 different metabolites in stem cells, the team discovered that high uptakes of ascorbate were one of the main metabolic features of human and mouse haematopoietic stem cells (HSCs).

People obtain ascorbate exclusively through diet, but most other animals (including mice) synthesise ascorbate in the liver using the enzyme gulonolactone oxidase (GULO).

To test whether ascorbate regulates HSC function, the team examined GULO negative mice that are unable to synthesize ascorbate and just like humans needed to obtain ascorbate through diet.

Initially, the researchers reasoned loss of ascorbate would lead to loss of stem cell function, but instead discovered that stem cells gained function and that this increased risk of leukaemia.

The increased risk was found to be linked to ascorbate depletion limiting function of an enzyme known as Tet2.

The findings, say the authors, have important implications for people with clonal haematopoiesis that places them at higher risk of developing leukaemia.

“Our data suggest it is important for people with clonal hematopoiesis to get adequate dietary ascorbate to maximize residual Tet tumour suppressor function,” write the authors.

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