A team from the Welcome Trust Sanger Institute, headed by two Greek researchers, Dr. Konstaninos Tzelepis and Dr. George Vasiliou, in collaboration with joint project leader Dr. Kosuke Yusa, have made an incredible breakthrough in the fight against one the most aggressive types of cancer, acute myeloid leukaemia (AML). In research published in “Cell Reports”, the team identified a large number of genes that could serve as potential targets for anti-AML treatments and describe how inhibition of one of these genes, KAT2A, destroys AML cells without harming non-leukaemic blood cells. The team used CRISPR-Cas9 gene-editing technology to screen cancer cells for vulnerable points. This technology can be used to disrupt and destroy targeted genes in the genomes of cells. To achieve their goals, the team refined a CRISPR-Cas9 technique to efficiently disrupt all genes in the leukaemia cell genome individually. This allowed them to identify those genes whose disruption was detrimental to the growth and survival of AML cells.

Dr Konstantinos Tzelepis, a first author on the paper from the Sanger Institute, said: “This is an exciting finding, as KAT2A inhibition worked on a number of primary AML cells with diverse genotypes. Whilst the gene needs to be studied in greater depth to understand its potential for use in the clinic, we show that targeting KAT2A destroyed AML cells in the laboratory while sparing healthy blood cells.”

Dr Konstantinos Tzelepis

The team then validated this finding, by disrupting the KAT2A gene from leukaemia cells in transgenic mice, and observing the effect on the cancer. They found that the mice lived longer when the KAT2A gene was disrupted.

Dr. Kosuke Yusa
Dr George Vassiliou, joint project leader from the Sanger Institute and Consultant Haematologist at Cambridge University Hospitals NHS Trust, said: “This research has led to the identification of many potential gene targets for future AML therapy, which we are making available to other researchers to explore. Whilst KAT2A inhibition now needs to be investigated as a treatment strategy for acute myeloid leukaemia, there are many more candidates to pursue by the leukaemia research community. Our hope is that this work will lead to more effective treatments against AML that will improve both the survival and the quality of life of patients.”

Dr George Vassiliou