Epigenome tags aggressive leukemias
An international team of researchers looking at the epigenome of people with adult B-acute lymphoblastic leukemia (ALL) has found changes that could be used as biomarkers to predict how the disease will develop. These could also be used as targets for new drugs.
B-acute ALL is generally very curable in children, but in adults it can be aggressive and is usually fatal. This may be because it is linked in with more genetic alterations in adults.
The researchers screened the epigenomes of 215 samples from adults with B-acute ALL, taken during diagnosis as part of a large Phase III trial. The genetic variations led to the production of altered proteins that drive the leukemic cells, and changes in the epigenome often linked in with these proteins, and so could be used as biomarkers.
Some of the altered proteins also "reprogrammed" the epigenetic settings on the surface of the DNA molecule, making the cells produce oncoproteins that help the leukemic cells to proliferate and survive. By inhibiting some of the proteins, the researchers were able to kill the leukemic cells. The results were published in Cancer Discovery.
The next step is to use the epigenetic biomarkers to select the patients with the worst disease in the next set of clinical trials, and to develop inhibitors as therapeutics.
"These results will ultimately lead to biomarkers that help guide treatment and to the development of therapies that will be more effective for patients with this aggressive form of leukemia," says Ari Melnick of Weill Cornell Medical College.
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