Researchers at Karolinska Institutet in Sweden and Kyoto University in Japan have identified new subgroups of the blood cancer acute myeloid leukaemia. The study, published in the journal Nature, shows that changes in the regulation of genes within cells can help explain the variation in the disease and influence prognosis and treatment choices.
Acute myeloid leukaemia (AML) is an aggressive form of blood cancer in which immature blood cells grow uncontrollably. Despite extensive knowledge of the genetic alterations underlying the disease, it is still difficult to fully understand why patients develop different disease courses. In this study, the researchers analysed so-called epigenetics – how genes are regulated without changes to the DNA sequence.
Divides leukaemia into subgroups
The study includes 1,563 patients in Sweden and Japan. The researchers used a method that measures how accessible DNA is within the cell nucleus, indicating which genes may be active. Based on these measurements, they were able to divide AML into 16 different groups with distinct molecular and biological characteristics.
“Our results show that, based on epigenetic analyses, leukaemia can be divided into new biologically relevant subgroups that provide more information than genetic analyses alone,” says Sören Lehmann, professor at the Department of Medicine, Huddinge, Karolinska Institutet.
By combining several types of data, including gene expression, DNA methylation and analyses of individual cells, the researchers were able to show that each group has its own patterns of gene regulation, cell differentiation and disease progression. They also found that these epigenetic groups were, in some cases, more closely associated with patient survival than current classification systems.
Different reactions to drugs
The study also shows that different groups of AML may respond differently to drugs. In analyses of 250 drugs, differences in sensitivity were observed that could be associated with the different epigenetic groups.
“This suggests that epigenetic changes may also influence how patients respond to treatment,” says Sören Lehmann.
The researchers emphasise that the results do not replace the current genetic classification of AML, but can complement it and contribute to more personalised treatment in the future. At the same time, further studies are needed to confirm the findings and to investigate how they can be used in clinical practice.
The study was carried out in collaboration between research groups in Sweden and Japan. It was funded, among others, by research councils and national research programmes in Japan and Sweden. See the scientific article for information on conflicts of interest.
Source: Karolinska Institutet