Preclinical study leads to potential improvement of effective leukaemia treatments, reduced chemotherapy side effects

The effectiveness of first-line treatments for leukaemia would potentially increase by blocking the production of a particular protein in the body, new study shows. Researchers have found the protein, called chromodomain helicase DNA-binding protein 4, or CHD4, can aid further improvement of treating acute myeloid leukaemia, and reduce the side effects of chemotherapy.

Acute myeloid leukaemia, or AML, is a lethal blood cancer that is commonly affecting older adults. Researchers at VCU Massey Cancer Centre, in the U.S., conducted preclinical experiments that successfully show the depletion of the CHD4 protein can make AML cells more sensitive to standard chemotherapy agents.

Blocking the production of the CHD4 protein reduced the ability of the cells to repair DNA damage and to grow again. In addition, depletion of CHD4 has helped healthy bone marrow cells not to be more sensitive to chemotherapy agents and reduced the side effects of the treatment to the patient.

"Targeting the CHD4 protein could allow us to reduce chemotherapy doses, which could potentially mean more effective first- and second-line treatments with fewer serious side effects," said Dr Gordon Ginder, director of Massey Cancer Centre and lead author of the study, in a press release.

The study, recently published in the journal Blood, also shows the ability of AML cells to form colonies has been severely restricted by blocking CHD4 in preclinical laboratory and animal models. CHD4 is an enzyme capable to stop tumour suppressor genes in cancer cells.

The procedure caused AML cells to be more sensitive to daunorubicin and cytarabine, the chemotherapy agents used for standard initial AML treatment. However, more studies are needed to look for potential ways to target CHD4, researchers said.

Future studies will aim to see the detailed mechanism of how CHD4 could reduce the ability of AML cells to initiate leukaemia, Ginder said. He added that the protein could be used for the development of future drugs.

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