New genes associated with relapse of acute myeloid leukemia

2022-01-13

In the blood cancer type acute myeloid leukemia, it is common that patients relapse some time after treatment. Researchers from IGP have in a new study identified genes that seem to be associated with the risk of relapse. The findings may form the basis for new treatment strategies and contribute to better survival for patients with acute myeloid leukemia.

Acute myeloid leukemia, AML, is one of the most common forms of leukemia in adults but it can also affect children. In most AML patients therapy results in complete disease remission but relapses within a few years are common and the relapsed patients often fail to respond to treatment.

AML is caused by genetic changes that cause certain types of white blood cells to grow abnormally. The genetic changes also affect the development of the disease and how it responds to treatment. To be able to develop new treatment strategies, one needs to identify the altered genes and based on their function, the processes in the cells that drive tumour development and therapy resistance. In the current study, the researchers have identified such genes.

“To gain knowledge on why the disease relapses it is important to study what happens in the tumour with time. To this end, we studied samples that were taken from the same patients both at diagnosis and at relapse. We found genes that had higher or lower activity in samples taken at relapse, as compared to the previous samples, and therefore are likely to be associated with the relapse,” says Linda Holmfeldt who has led the study.

The researchers also used machine learning-based analyses to find patterns in the activities of the identified genes. For instance, they found that increased activity for the gene CD6, in combination with decreased activity of the INSR gene, was associated with disease relapse.

Several of the identified genes appear to promote a pro-inflammatory tumour environment. A novel strategy for treating AML could therefore be to target key regulators of pro-inflammatory pathways.

“One could envision the development of therapies that target the proteins encoded by the genes that we have found. This could also potentially result in personalized therapies that are adjusted to whether the genes are active or not in individual patients. But this will require further studies,” says Linda Holmfeldt.

The study is a collaboration with researchers at the Department of Medical Sciences and Department of Women’s and Children’s Health at Uppsala University, Karolinska Institutet, Umeå University, University of Gothenburg, and universities in Oslo, Helsinki, Aarhus, Warsaw and Seattle, and has been published in the journal Blood Advances.

More information:
Paper in Blood Advances
Linda Holmfeldt’s research