A study led by the University of Birmingham has made a breakthrough in the understanding of how different genetic mutations cause acute myeloid leukaemia.
One of the most common acute leukaemia’s in adults with around 2,400 people in the UK diagnosed with the disease each year, the survival rates for those diagnosed with acute myeloid leukaemia are very poor and new treatments are needed.
Researchers at the Universities of Birmingham and Newcastle worked in collaboration to study the DNA of two types of acute myeloid leukaemia in an effort to explain how clinical prognosis can differ.
‘It has been known for a long time that acute myeloid leukaemia is highly heterogeneous, involving different disease-causing genetic mutations.
‘This in turn leads to highly variable clinical outcomes, with some patients responding better to certain treatments than others.
‘Prior to this study, the reason for the differences in response to treatment was unknown.
‘We discovered how two closely related oncogenes – genes which have the potential to cause cancer – differently reprogram blood stem cells in acute myeloid leukaemia and send them spiralling out of control.’
The study, published today in Cell Reports, highlights the difficulties faced in understanding the heterogeneity of the disease.
Dr Justin Loke, a Kay Kendall Clinical Fellow from Birmingham Queen Elizabeth Hospital’s Haematology Department which is affiliated with the University of Birmingham’s Institute of Cancer and Genomic Sciences, added:
‘We used state-of-the-art molecular technology that studies all genes within leukaemic cells to investigate why two types of the disease with mutations in the same gene display a completely different clinical profile.
‘We showed that the maintenance of the leukaemic state of these two types of acute myeloid leukaemia is dependent on different sets of normal genes, therefore identifying a route to developing tailored and personalized treatments for patients with different cancer-causing mutations in order to specifically target each tumour.’
Since the early 1990s, acute myeloid leukaemia incidence rates have increased by more than a quarter (28 per cent) in the UK. One in 200 men and one in 255 women will be diagnosed with acute myeloid leukaemia during their lifetime.
The study was funded by the Kay Kendall Leukaemia Fund and Bloodwise. Bloodwise, the UK’s specialist blood cancer charity, funds world-class research and offers expert information and support to anyone affected by leukaemia, lymphoma, myeloma and other blood cancer related disorders.
The Kay Kendall Leukaemia Fund was established in 1984 under the Will of the late James Sainsbury CBE. It awards grants for research on aspects of leukaemia and for relevant studies on related haematological malignancies.
For further information or interviews contact:
Emma McKinney, Communications Manager, University of Birmingham, at +44 (0)121 414 6681
Notes to Editors
• Loke et al. (2017). ‘RYBX1-ETO and RUNX1-EVI1 Differentially Reprogram the Chromatin Landscape in t(8;21) and t(3;21) AML’ DOI is: 10.1016/j.celrep.2017.05.005
• Justin Loke,1,4 Salam A. Assi,1,4 Maria Rosaria Imperato,1 Anetta Ptasinska,1 Pierre Cauchy,1 Yura Grabovska,2 Natalia Martinez Soria,2 Manoj Raghavan,1 H. Ruud Delwel,3 Peter N. Cockerill,1 Olaf Heidenreich,2 and Constanze Bonifer1,5,*
1Institute for Cancer and Genomic Sciences, College of Medicine and Dentistry, University of Birmingham, B15 2TT Birmingham, UK
2Northern Institute for Cancer Research, University of Newcastle, Newcastle upon Tyne NE2 4HH, UK
3Department of Hematology, Erasmus University Medical Center, Dr. Molewaterplein 50, 3015 GE Rotterdam, the Netherlands
4These authors contributed equally
• To access the research paper log onto: http://www.cell.com/cell-reports/fulltext/S2211-1247(17)30611-3
University of Birmingham