Exploring new therapies for acute myeloid leukemia
A CRISPR/Cas9-based screen to look for genes that are essential for the survival of leukemic cells.
In this paper, published at the magazine Blood, (The American Society of Hematology) the authors have studied the blood cancer acute myeloid leukemia (AML). Since most AML patients experience relapse after initial treatment, scientists from the Helin group (BRIC/DanStem) performed a CRISPR/Cas9-based screen to look for genes that are essential for the survival of leukemic cells. Their aim was to identify proteins that could be targeted for the development of new therapies.
While we have a good understanding on how the disease develops and progresses, the current treatment methods are not curative.
The group found that the protein Rio-kinase 2 (RIOK2) is essential for the survival of leukemic cancer cells. They discovered that if they remove RIOK2 in the leukemic cells either by the use of genetic tools or by pharmacological inhibition, the cancer cells start to die. They have validated these results both using cancer cell lines in the petri dish, as well as in mouse blood cancer model. When RIOK2 is removed or its function is inhibited, the leukemic cells stop making new proteins. They found that ribosomes, which are the cellular machineries that make proteins in the cell are actively degraded when they remove RIOK2.
Interestingly, when they removed RIOK2 in a different cell type called fibroblasts, they saw that these cells were much less affected by the removal of RIOK2 compared to the leukemic cells. This indicates that there might be different mechanisms with how the cells deal with the loss of RIOK2 in ways that are not well understood at the moment.
Possible consequences for patients
As RIOK2 is essential for the survival of leukemic cells, inhibition of RIOK2 function can be used to kill leukemic cancer cells. The scientists are currently investigating whether the inhibition of RIOK2 can be used as a therapy in acute myeloid leukemia.
Image: Identification of RIOK2 as a new therapeutic target in AML
The first author of this study is Copenhagen Bioscience PhD student Jan-Erik Messling. Jan-Erik is currently finishing up his studies.
Messling, J. E., Agger, K., Andersen, K. L., Kromer, K., Kuepper, H. M., Lund, A. H. and Helin K. (2021) Targeting RIOK2 ATPase activity leads to decreased protein synthesis and cell death in acute myeloid leukemia. Blood. doi: 10.1182/blood.2021012629.