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Genetics Allows Personalized Disease Predictions for Chronic Blood Cancers

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Thursday, October 11, 2018

CAMBRIGE, UK - Scientists have developed a successful method to make truly personalised predictions of future disease outcomes for patients with certain types of chronic blood cancers. The study from the Wellcome Sanger Institute, the Wellcome-MRC Cambridge Stem Cell Institute, the University of Cambridge, and their collaborators, combined extensive genetic and clinical information to predict the prognosis for patients with myeloproliferative neoplasms. The research also identified eight different genetic subgroups of the disease that link with patterns of clinical disease and patient prognosis.

Published in the New England Journal of Medicine, this work could lead to personalised medicine for patients with these blood cancers. It will help doctors identify those patients who are likely to have a very good future outlook, and which patients may benefit from specific treatments or clinical trials.

Research Article:
Classification and Personalized Prognosis in Myeloproliferative Neoplasms. N Engl J Med 2018; 379:1416-1430
DOI: 10.1056/NEJMoa1716614

Myeloproliferative neoplasms are a group of blood cancers affecting around 30,000 patients in the UK. These cancers are chronic, long term conditions and patients suffer from a risk of blood clots and bleeding. In addition, these cancers can progress to more advanced forms of disease, including acute leukaemia, that have a poor outlook. It is important to patients to know how their disease is likely to progress in the future, but it has not previously been possible to provide personalised predictions for each individual patient.

The current classification system for these blood cancers was created in the 1950s when myeloproliferative neoplasms were divided into three clinical types. However, there are known to be challenges with this classification system. This lack of accurate classification can make it difficult for doctors to decide on the most appropriate treatment for patients and to provide information on future outlook.

To understand the biological factors causing myeloproliferative neoplasms the researchers studied 69 cancer genes from over 2,000 patients with these blood cancers. Using this genetic information, they found there were eight different subtypes of these cancers. These genetic subtypes were also found to be clinically different from each other, indicating that the researchers had identified real differences between patient groups.

Combining the genetic information for each person with their clinical information, the researchers were then able to develop a method to make personally tailored disease predictions for individual patients suffering from these cancers. They found this personalised method outperformed all current schemes available to make disease predictions and had the additional advantage of giving patient-specific predictions, rather than simply classifying patients into broad risk categories.

Dr Jyoti Nangalia, a first author on the study from the Wellcome Sanger Institute, said: "Despite some knowledge of the risks of myeloproliferative neoplasms we have been unable to make accurate personal predictions for individual patients. Our new online calculator takes genetic and clinical information available for a patient and makes a prediction of the future outcome of that particular person's disease. In the future this could be used to reassure patients who have a good predicted outcome, and identify patients who are at risk of developing severe disease who could benefit from an alternative treatment approach."

Professor Tony Green, a senior author on the paper from the Wellcome-MRC Cambridge Stem Cell Institute and the University of Cambridge, Department of Haematology, said: "This work represents a step change in our understanding of the myeloproliferative neoplasms. Not only does it reveal a new classification based on causal mechanisms but it also provides for the first time personally-tailored predictions to guide patient management."

The study also revealed that some subgroups shared features with other blood cancers. This work could bring clarity to disease classification of blood cancers in the future and enable the development and testing of new treatments.

Dr Peter Campbell, a senior author from the Wellcome Sanger Institute, said: "This research proves the potential of personalised medicine, using genetics. Modern genomics will empower clinicians and support their decisions regarding the best therapies and clinical trials for each patient. We hope our study will be a game changer for patients with these blood cancers by providing better predictions for how their disease may behave in the future, and inform treatment choice."

About Myeloproliferative neoplasms:
Myeloproliferative neoplasms are a group of rare disorders of the bone marrow that cause an increase in the number of red or white blood cells or platelets. The aim of treatment is usually to control symptoms rather than cure the condition. More info about these blood cancers is available from Cancer Research UK website: https://www.cancerresearchuk.org/about-cancer/other-conditions/myeloproliferative-neoplasms

Selected Websites:
Wellcome-MRC Cambridge Stem Cell Institute The Cambridge Stem Cell Institute is a world-leading centre for stem cell research with a mission to transform human health through a deep understanding of stem cell biology. Our scientists study stem cell behaviour, both normal and pathological, and use their findings to improve the prevention, diagnosis and treatment of diseases. http://www.stemcells.cam.ac.uk/ Follow @SCICambridge

University of Cambridge
The mission of the University of Cambridge is to contribute to society through the pursuit of education, learning and research at the highest international levels of excellence. To date, 98 affiliates of the University have won the Nobel Prize. Founded in 1209, the University comprises 31 autonomous Colleges, which admit undergraduates and provide small-group tuition, and 150 departments, faculties and institutions. Cambridge is a global university. Its 19,000 student body includes 3,700 international students from 120 countries. Cambridge researchers collaborate with colleagues worldwide, and the University has established larger-scale partnerships in Asia, Africa and America. The University sits at the heart of one of the world's largest technology clusters. The 'Cambridge Phenomenon' has created 1,500 hi-tech companies, 14 of them valued at over US$1 billion and two at over US$10 billion. Cambridge promotes the interface between academia and business, and has a global reputation for innovation. http://www.cam.ac.uk/

The Wellcome Sanger Institute
The Wellcome 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. To celebrate its 25th year in 2018, the Institute is sequencing 25 new genomes of species in the UK. Find out more at http://www.sanger.ac.uk or follow @sangerinstitute

Wellcome
Wellcome exists to improve health for everyone by helping great ideas to thrive. We're a global charitable foundation, both politically and financially independent. We support scientists and researchers, take on big problems, fuel imaginations and spark debate. http://www.wellcome.ac.uk

Contact:
Samantha Wynne
press.office@sanger.ac.uk
0044-122-349-2368

Source: Wellcome Trust Sanger Institute
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