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, according to a new study on the genetics of AML in New England Journal of Medicine.
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.
Researchers studied 1540 patients with AML that were enrolled in clinical trials. They analyzed more than 100 genes known to cause leukemia, to identify common genetic themes behind the development of the disease. They 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 leukemia. 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 leukemia 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 leukemia down the microscope, but we find extensive differences between those leukemias 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.
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.
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."