Greek doctors leading a team from the Wellcome Trust Sanger Institute in the UK, outside Cambridge, have made an incredible breakthrough discovery in the fight against acute meloid leukemia (AML). Dr. Konstantinos Tzelepis and Dr. George Vassiliou — the Greek researchers heading the team — in collaboration with joint project leader Dr. Kosuke Yusa, identified a large number of genes that could act as potential targets for anti-AML treatments. Their research paper, published in “Cell Reports,” describes how the repression of KAT2A, one of the genes, destroys AML cells without destroying non-leukemic 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 leukemia cell genome individually. This allowed them to identify those genes whose disruption was detrimental to the growth and survival of AML cells.
“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,” said Dr. Tzelepis who validated findings on transgenic mice and observing the effect on the cancer. The mice lived longer when the KAT2A gene was disrupted.
“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 leukemia, there are many more candidates to pursue by the leukemia 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,” said Dr. Vassiliou.