Peroxidasin is a protein found in most tissues in the human body. Its physiological function was discovered only recently and so far its contribution to health... read more
Developing tools to identify ascorbate-responsive subgroups of acute myeloid leukaemia
Acute myeloid leukaemia (AML) is a particularly aggressive form of blood cancer. Chemotherapy and bone marrow transplant can result in a period of clinical remission, but overall only 20% of patients survive for more than 5 years. Furthermore, many patients do not respond to chemotherapy at all, indicating that new treatment strategies are needed.
Many of the early genetic changes in the development of AML affect epigenetic regulation, with effects that are potentially reversible. A prime example is the epigenetic regulator TET2, a protein whose activity is affected in up to one third of AML patients. TET2 requires vitamin C (ascorbate) to function, and patients with decreased TET2 activity could benefit from ascorbate supplementation. Recent studies using mouse models support this hypothesis.
However, patients with TET2 mutations always have additional mutations, which can greatly affect response to treatment. The effective design of future clinical trials relies on targeting the right treatment to the appropriate combination of mutations.
Therefore, we will develop AML cell lines that combine TET2 mutations with additional mutations seen in patients to investigate their response to treatment with ascorbate. These cell lines will be invaluable tools for identifying subgroups of AML patients that could respond to ascorbate.
Dr Das is interested in the role that metabolism and epigenetics play in the development of cancer. Together with Professor Margreet Vissers, he is currently investigating the potential use of ascorbate (vitamin C) as an epigenetic therapeutic for specific subtypes of acute myeloid leukaemia (AML).More About Dr Andrew Das