New test for chronic blood cancers

Identification of a gene that underlies 40 per cent of patients with specific blood cancer leads to better diagnosis tool

DOI: 10.1056/NEJMoa1312542

Mutational profile of 151 samples of this group of blood diseases. Number of cases identified to have mutations in recurrently mutated genes and in genes previously implicated in these diseases.

Researchers have discovered that the gene CALR is mutated in 40 per cent of patients with a certain group of chronic blood cancers. On the back of this finding, they are now developing a test that will soon be able to catch the vast majority of these blood cancers.

Although around 60 per cent of cases can be identified with an existing blood test, scientists did not know what caused the other cases and therefore could not test for it. The team’s result will mean that the other 40 per cent of patients with the disease will now be able to avoid invasive and painful procedures before diagnosis.

This group of chronic blood cancers – which affect an estimated 30,000 people annually in the UK – cause the over-production of red blood cells and platelets. These changes result in an increased incidence of blood clots which can be devastating when strokes or heart attacks occur. Although many patients can live for years with few if any symptoms, in some patients the disorders can become more aggressive with time and may even develop into acute leukaemia.

“There is now a sense of completeness with these disorders – the vast majority of our patients can now have a definitive genetic diagnosis made. In the next year or two, we will see these genetic technologies increasingly used in the diagnosis of all cancers, especially blood cancers.”

Dr Peter Campbell co-lead author from the Wellcome Trust Sanger Institute

In 2005 scientists identified that mutations to the JAK2 gene are associated with around 60 per cent of blood cell disorders. Based on these findings a blood test was developed that transformed the way these blood disorders are diagnosed. Unfortunately Because the gene was only found in a little over half of people with chronic blood cancers, individuals who tested negative for the JAK2 gene would then have to undergo a battery of protracted, invasive testing to determine if they had one of these disorders.

“Diagnosing these chronic blood cancers is currently difficult and requires multiple tests, some of which are invasive and painful. Now, most patients with a suspected blood cancer will be able to be given a diagnosis after a simple blood test.”

Professor Tony Green, co-lead author from the University of Cambridge’s Cambridge Institute for Medical Research and Department of Haematology

The team sequenced the DNA of patients with chronic blood disorders. By analysing the DNA sequence, they were able to identify CALR as a gene that underlies cancer. When mutated, CALR results in chronic blood cancers. Additionally, they found that patients with the CALR mutation – unlike those with the JAK2 mutation – had higher platelet counts and lower haemoglobin levels.

“Not only will the identification of CALR lead to a new, less invasive test, we also hope that it can lead to new treatments – just as the discovery of JAK2 did. The CALR gene is involved in a cell function – aiding with the folding of proteins made by the cell – which has not been implicated in these disorders before, so our research raises as many questions as it answers.”

Dr Jyoti Nangalia Co-first author of the study from the University of Cambridge

More information

Funding

A full list of funding can be found on the paper

Participating Centres

• Cambridge Institute for Medical Research and Wellcome Trust/MRC Stem Cell Institute, University of Cambridge, Cambridge, United Kingdom
• Wellcome Trust Sanger Institute, Hinxton, Cambridge, United Kingdom
• Department of Haematology, University of Cambridge, United Kingdom
• Department of Haematology, Addenbrooke’s Hospital, Cambridge, United Kingdom
• University of Cambridge Metabolic Research Laboratories and NIHR Cambridge Biomedical Research Centre, Cambridge, United Kingdom
• Department of Human Genetics, VIB and KU Leuven, Leuven, Belgium
• Faculty of Medicine, University of Southampton, Southampton, United Kingdom
• Dipartimento di Medicina Sperimentale e Clinica, University of Florence, Florence, Italy
• Guy’s and St Thomas’ NHS Foundation Trust, Guy’s Hospital, London, United Kingdom
• Department of Haematology, University Hospital Southampton, Southampton, United Kingdom
• Department of Hematology, Ninewells Hospital, Dundee, United Kingdom
• Division of Molecular Histopathology, Department of Pathology, University of Cambridge, United Kingdom
• Haemato-Oncology Research Unit Division of Molecular Pathology The Institute of Cancer Research, United Kingdom
• St James Institute of Oncology, St James Hospital, Leeds, United Kingdom
• Leukaemia & Lymphoma Research