A group of researchers at the Cambridge Institute for Medical Research found that the epigenetic protein delayed the development of AML. However, the epigenetic protein was found to have changed sides once the cancer is established, by helping in maintaining the growth of tumor.
Published in the Journal of Experimental Medicine, the study indicates that targeting EZH2 could help in the effective treatment of the aggressive form of blood cancer.
As per the scientists, EZH2 can regulate the activity of several genes by chemical modification of the histone proteins that constitute the cell’s DNA.
Surges in EZH2 activity are thought to lead to the development of various human tumors such as breast and prostate cancers. Currently, various clinical trials are probing if drugs that prevent EZH2 from modifying histones can be used for the treatment of cancer.
However, scientists are yet to establish if EZH2 also promotes the development of blood cancers like AML. There is some evidence though that indicates the epigenetic protein could actually prevent myeloid malignancies like AML.
The research team involved in the study observed that mice having less content of EZH2 developed AML much quicker than otherwise, which suggests that the epigenetic protein indeed does delay the development of AML.
After AML had fully developed and established itself in the animal, removing the EZH2 gene or blocking the EZH2 protein with a drug disrupted growth of tumor and prolonged its survival by a significant extent. The researchers found that inhibiting EZH2 also blocked the growth of the AML cells, which were isolated from patients.
The team also observed that blocking EZH2 has conflicting impact on the development and maintenance of AML as the protein has almost full control over various sets of genes at both early and late stages of the cancer.
Cambridge Institute for Medical Research, UK, Brian Huntly, who led the researchers team, said: “Our findings uncover novel and dramatically opposing functions of EZH2 during AML that appear dependent upon the phase of disease, with EZH2 functioning as a tumor suppressor in AML induction and as a facilitator of disease in established AML.
“To our knowledge, this is the first description of an epigenetic regulator having both tumor-suppressive and oncogenic function in different phases of the same cancer. In addition, our work validates EZH2 as a therapeutic target with the potential to treat several different subtypes of AML.”