New gene discovered in human stem cells may benefit transplant patients
27 April 2007
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.
Dr Rajeev Gupta, a Leukaemia Research-funded consultant haematologist, has uncovered that the gene Nephroblastoma Overexpressed (Nov) plays a key role in regulating the production of blood from stem cells. The work, which was carried out in the MRC Molecular Haematology Unit, is published in the journal Science.
Stem cells are vital for normal blood production and are used in transplants in patients with leukaemia and other blood cancers.
Dr Gupta 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.”
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.”
Notes for Editors:
1. R. Gupta, D. Hong, F. Iborra, S. Sarno, T. Enver, NOV (CCN3) Functions as a Regulator of Human Hematopoietic Stem or Progenitor Cells, Science, 316, 5823 (2007)
2. Dr Gupta’s work is part of a £1,272,483 Leukaemia Research programme based at the Medical Research Council Molecular Haematology Unit, Weatherall Institute of Molecular Medicine, University of Oxford, and led by Professor Tariq Enver.
3. Leukaemia Research currently has around £8million invested in stem cell-related research. Over the next five years, Leukaemia Research urgently needs to raise over £100million to commit to new research. From basic laboratory research to clinical trials with patients, Leukaemia Research is committed to saving lives by funding high quality, carefully selected research throughout the UK. Leukaemia Research is the only national charity devoted exclusively to improving treatments, finding cures and learning how to prevent leukaemia, Hodgkin's lymphoma and other lymphomas, myeloma and the related blood disorders, diagnosed in 24,500 people in the UK every year. Further information, including patient information booklets, is available from www.lrf.org.uk.
4. The MRC Molecular Haematology Unit was founded in 1980 and is located in the Weatherall Institute of Molecular Medicine. It includes eight research teams with a total of about seventy scientists who share a common interest in understanding the process by which multipotential haemopoietic stem cells become committed and differentiate into the highly specialised cells found in blood. The research programme led by Professor Enver attempts to understand, at the molecular level, how blood stem cells decide whether to self-renew or to differentiate and, in the latter case, into which cell type (a process termed lineage-specification). These 'working decisions' that stem cells make are ultimately effected at the level of differential gene activity or usage, and gaining an understanding of how this process works is an important problem in developmental biology, transplantation medicine, stem cell-based gene therapy and haematological malignancy.
5. The Medical Research Council is dedicated to improving human health through excellent science. It invests on behalf of the UK taxpayer. Its work ranges from molecular level science to public health research, carried out in universities, hospitals and a network of its own units and institutes. The MRC liaises with the Health Departments, the National Health Service and industry to take account of the public’s needs. The results have led to some of the most significant discoveries in medical science and benefited the health and wealth of millions of people in the UK and around the world. www.mrc.ac.uk
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