Sanger Institute: Landmark study shows AML is at least 11 different diseases

Scientists at the Wellcome Trust Sanger Institute and their international collaborators have shown that Acute Myeloid Leukaemia (AML) is not a single disorder, but at least 11 different diseases, and that genetic changes explain differences in survival among young AML patients. Published in the New England Journal of Medicine, the ground-breaking study on the genetics of AML could improve clinical trials and the way patients are diagnosed and treated in the future.

In the largest study of its kind, researchers studied 1540 patients with AML that were enrolled in clinical trials. They analysed more than 100 genes known to cause leukaemia, to identify common genetic themes behind the development of the disease.

The researchers found that the patients were divided into at least 11 major groups, each with different constellations of genetic changes and distinctive clinical features. Despite finding common themes however, the study also showed that most patients had a unique combination of genetic changes driving their leukaemia. This genetic complexity helps explain why AML shows such variability in survival rates among patients.

Full knowledge of the genetic make-up of a patient's leukaemia substantially improved the ability to predict whether that patient would be cured with current treatments. This information could be used to design new clinical trials to develop the best treatments for each AML subtype, with the ultimate aim of bringing more extensive genetic testing into routine clinical practice.

Dr Peter Campbell, co-leader of the study from the Wellcome Trust Sanger Institute, said: "This is our first detailed look at how the genetic complexity of a cancer impacts on its clinical outcomes. Two people may have what looks like the same leukaemia down the microscope, but we find extensive differences between those leukaemias at the genetic level. These genetic differences can explain so much of why one of those patients will be cured, while the other will not, despite receiving the exact same treatment.

"We have shown that AML is an umbrella term for a group of at least 11 different types of leukaemia. We can now start to decode these genetics to shape clinical trials and develop diagnostics."

Acute myeloid leukaemia (AML) is an aggressive blood cancer that affects people of all ages, often requiring months of intensive chemotherapy in hospital. It develops in cells in the bone marrow.

This study shows that by using a comprehensive approach, scientists will be able to understand the complex interplay between the genetic changes seen in a cancer and the clinical outcomes of that cancer. This requires full genetic analysis of samples from large numbers of patients matched with detailed information about the treatment and survival of those patients. Further research into leukaemia, and indeed other cancers, will allow researchers to understand the patterns of how the disease develops and how patients are going to respond to treatment.

Prof. Hartmut Döhner, Medical Director of Hematology/Oncology at Ulm University and chair of the German-Austrian AML Study Group, said: "This landmark study has showcased the importance of international collaboration between academic institutions and clinical trials and the large scale of the study. These results represent a major step forward in translating the exciting findings from molecular genetics into better disease classification, diagnosis, and improved care of our patients with acute myeloid leukaemia."

Dr Elli Papaemmanuil, joint first author from the Sanger Institute and the Memorial Sloan Kettering Cancer Centre in New York, said: "Leukemia is a global problem with poor outcomes for most patients. We combined detailed genetic analysis with patient health information to help understand the fundamental causes of AML. For the first time we untangled the genetic complexity seen in most AML cancer genomes into distinct evolutionary paths that lead to AML. By understanding these paths we can help develop more appropriate treatments for individual patients with AML. We are now extending such studies across other leukaemias."

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Notes to Editors:

About Acute Myeloid Leukaemia:

  • Acute myeloid leukaemia (AML) is a type of blood cancer that develops when the cells in the bone marrow that produce myeloid cells become cancerous. As blood cells are made in the bone marrow, the cancer will be present in the bone marrow and in the blood.
  • Every day we make around 10 billion new blood cells, and the information which controls how these blood cells reproduce is held within our DNA. Every time a cell divides, the entire DNA code has to be copied exactly, and mistakes are made by chance. AML develops when there are a series of errors in the DNA. It usually takes mistakes in several key genes that control blood production to cause AML.
  • There were around 2,900 new cases of acute myeloid leukaemia (AML) in the UK in 2013, that's around 8 cases diagnosed every day (CRUK figures).
  • Worldwide, 351,965 people were estimated to have AML in 2012 (GLOBOCAN figures).

For more information on AML please see: https://bloodwise.org.uk/understanding-blood-cancers/what-acute-myeloid-leukaemia-aml

More details about the AML study group can be found at: https://www.uni-ulm.de/onkologie/AMLSG/studien.html

Publication: E. Papaemmanuil and M. Gerstung et al. (2016). Genomic classification and prognosis in acute myeloid leukemia. New England Journal of Medicine.

Funding: The work was supported by the Wellcome Trust, Bundesministerium fur Bildung und Forschung, Deutsche Krebshilfe and Deutsche Forschungsgemeinschaft, the European Hematology Association, Amgen and the Kay Kendall Leukaemia Fund.

Selected websites:

Memorial Sloan Kettering Cancer Centre, New York

We are the world's oldest and largest private cancer center, home to more than 14,000 physicians, scientists, nurses, and staff who are united by a relentless dedication to conquering cancer. As an independent institution, we combine over 130 years of research and clinical leadership with the freedom to provide highly individualized, exceptional care to each patient. And our always-evolving educational programs continue to train new leaders in the field, here and around the world. With locations and partners in New York City and the tristate area, Memorial Sloan Kettering is also committed to ensuring that patients have access to the latest care in a convenient setting. http://www.mskcc.org.

Ulm University

Ulm University, the youngest university in Baden-Württemberg, was founded in 1967 as university for medicine and natural sciences. The subject spectrum has been expanded considerably since then. There are currently about 10,000 students enrolled across four Faculties ('Medicine', 'Natural Sciences', 'Mathematics and Economics', and 'Engineering, Computer Sciences and Psychology').

Ulm University is the centre of and driving force behind the Science City of Ulm, a dynamically growing research environment including hospitals, technology companies and other institutions. The University's research foci comprise life sciences and medicine, bio-, nano- and energy materials, financial services and their mathematical methods, as well as information, communication and quantum technologies. http://www.uni-ulm.de/en/homepage.html

Department of Internal Medicine III at Ulm University

The Focus of the Department of Internal Medicine III in patient care, research and teaching lies in hematological, oncological, infectious and rheumatologic diseases as well as palliative care for cancer patients. http://www.uniklinik-ulm.de/index.php?id=1453&L=1

EMBL-EBI

The European Bioinformatics Institute is part of EMBL, and is a global leader in the storage, analysis and dissemination of large biological datasets. EMBL-EBI helps scientists realise the potential of 'big data' by enhancing their ability to exploit complex information to make discoveries that benefit mankind. We are a non-profit, intergovernmental organisation funded by EMBL's 21 member states and two associate member states. Our 570 staff hail from 57 countries, and we welcome a regular stream of visiting scientists throughout the year. We are located on the Wellcome Genome Campus in Hinxton, Cambridge in the United Kingdom. http://www.ebi.ac.uk

The Wellcome Trust Sanger Institute

The Wellcome Trust Sanger Institute is one of the world's leading genome centres. Through its ability to conduct research at scale, it is able to engage in bold and long-term exploratory projects that are designed to influence and empower medical science globally. Institute research findings, generated through its own research programmes and through its leading role in international consortia, are being used to develop new diagnostics and treatments for human disease. http://www.sanger.ac.uk

The Wellcome Trust

The Wellcome Trust is a global charitable foundation dedicated to achieving extraordinary improvements in human and animal health. We support the brightest minds in biomedical research and the medical humanities. Our breadth of support includes public engagement, education and the application of research to improve health. We are independent of both political and commercial interests. http://www.wellcome.ac.uk

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