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New Gene Discovered in Human Stem Cells may Benefit Transplant Patients

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Oxford scientists have revealed a link between a gene and the activity of human blood stem cells, giving hope that stem cell transplant success for blood cancer patients may be significantly improved.

A team at the MRC Molecular Haematology Unit at Oxford University has found that a gene called ‘Nephroblastoma Overexpressed’ (known as Nov) plays a key role in regulating how much blood is produced from stem cells.

Stem cells are vital for normal blood production and are used in transplants in patients with leukaemia and other blood cancers. The findings, published in Science, raise the possibility of using the Nov gene to amplify the number of blood cells available. The work is funded by Leukaemia Research.

Dr Rajeev Gupta, a Leukaemia Research-funded consultant haematologist said: "The Nov gene makes a type of protein similar to a hormone. Such molecules often play important biological roles, and so four years ago when we first found that the gene is active in blood cells, including stem cells, we decided to study it in more detail.

"Switching off the Nov gene reduces stem cell activity and the production of blood cells falls. Conversely, when we added Nov protein to stem cells we increased the production of blood cells. This implies that the gene plays a key role in the regulation of blood production from stem cells,” he added.

Professor Tariq Enver, who leads the team at the MRC Molecular Haematology Unit in Oxford, said: "Of course genes never work alone and the next step of our work will focus on identifying the genetic pathway through which Nov works, i.e. finding out who Nov's friends are. Once these interactions have been established and we know whether Nov is the best gene to work with, we will be another step closer to devising better therapies for leukaemia patients.”

It is hoped that the discovery may in the future lead to Nov or a related gene playing a clinical role in stem cell transplants particularly in the context of cord blood.

"Cord blood donations contain sufficient numbers of stem cells to treat children but single donations are generally not enough for use in adults. We are actively pursuing whether Nov can amplify stem cells in cord blood. If so, cord blood could potentially be used more widely for the treatment of adult patients," said Professor Enver.

Dr Gupta added: "Nov and related genes certainly show great potential to play a role in future improvements for cancer patients treated with stem cell-based therapies, such as bone marrow transplants. We are actively working to transfer our laboratory work to the bedside."