Research led by Peter Mack and published in Cancer discovery A new combination treatment for acute myeloid leukemia (AML) has been found to be more effective in a preclinical study than any drug used alone.
Acute myelogenous leukemia (AML) is an aggressive type of leukemia. When a patient has acute myelogenous leukemia (AML), abnormal, immature white blood cells accumulate in the bone marrowIt inhibits the production of normal blood cells. In addition, these cancer cells are not able to fight the infection on their own.
In one of the regularly occurring types of AML, one of the drivers of the disease is a specific type of genetic abnormality.
A portion of the genome taken from one chromosome sticks together in a small portion of the genome from another chromosome — two genes fused together to form new gene This does not happen in nature,” says Professor Peter McRicky Johnston, co-lead author of the research.
As a result of this genetic fusion, genes that should be turned off are now turned on and vice versa – leading to leukemia.
The researchers were looking at how to prevent this from happening, as a way to develop new treatments against acute myelogenous leukemia (AML) that are insensitive to conventional chemotherapy.
In this study we used a file medicine called Histone deacetylase inhibitor This dampens the dysregulated cell response and slows the growth of leukemia cells,” says Dr. Peter Mack, Dr. Pilar Dominguez, the other lead author on the research.
“But it also had an additional effect that we didn’t expect.”
The drug caused one type of immune cell to produce a molecule called . Antivirus, which has been known for decades to also have anti-leukemia effects. It is also available as a drug approved by the Food and Drug Administration.
“By chance, the histone deacetylase inhibitor was also telling the body to produce its own interferon,” says Professor Johnston.
Interferon affects leukemia cells and eventually results in death cancer cellsDr. Dominguez says.
Based on these findings, the researchers designed an effective combination drug therapy consisting of a histone deacetylase inhibitor and interferon. This combination showed better anti-leukemia effects for those seen using either drug alone.
“We hope that this will translate into a new approach to treating AML,” says Dr. Dominguez.
Jessica M. Simon et al., Epigenetic activation of plasmatic DCs driving IFNAR-dependent therapeutic differentiation of AML, Cancer discovery (2022). DOI: 10.1158/2159-8290.CD-20-1145
Submitted by Peter McCallum Cancer Center
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