Newly discovered genetic abnormality affects leukemia prognosis

A number of genetic aberrations affect the development of AML. Researchers have identified different genes that are involved and that can be alter in different ways. Often mutations in the the gene result in the production of an abnormal, non-functional protein. However, sometimes large parts of the gene have been removed, resulting in deletions. The researchers have now shown that such deletions in the gene RUNX1 are more common than previously considered, and that they have a role in disease development.

“We analysed the genome from 60 patients with AML to see whether they had an abnormal RUNX1 gene and what kinds of alterations they contained. In one fourth of them we discovered deletions which is a large proportion and in fact more common than the classical mutations,” says Panagiotis Baliakas, researcher at the Department of Immunology, Genetics and Pathology, who led the study.

When physicians assess disease development for AML, they stratify the prognosis as favourable, intermediary or adverse. This is often based on which types of genetic alterations are present and the classical RUNX1 mutations are generally classified as having an adverse progonosis. When the researchers in the study investigated clinical symptoms in patients with RUNX1 deletions they found that these patients should also be stratified as adverse.

“When we evaluated how the patients had been stratified, we saw that some of those that had RUNX1 deletions should be classified as adverse instead of intermediary, which was the previous stratification. Our results show that if you would also consider RUNX1 deletions in the stratification it could be more effective. This is important since the stratification affects how you choose to treat the disease,” Baliakas says.

The researchers think that their findings are important both for future therapies for AML and for other diseases where RUNX1 is involved. They also argue in favour of studying how deletions in other genes affect the prognosis for other types of leukemia and also for cancer in general.

“This kind of genetic alteration is generally not detected with the standard sequencing technologies used in the health care, so it would be valuable with additional studies to determine how common it is,” Baliakas says.

The study has been published in the journal Clinical Cancer Research and is a collaboration with researchers the Department for Clinical Genetics and Department of Hematology, Uppsala University Hospital.

Kerstin Henriksson