Photo courtesy of VCU
Massey Cancer Center
Preclinical experiments have shown that blocking production of the protein CHD4 may help increase the effectiveness of first-line treatments for acute myeloid leukemia (AML).
Researchers found that depleting AML cells of CHD4 makes them more susceptible to standard chemotherapeutic agents by reducing the cells’ ability to repair DNA damage.
Depleting CHD4 also decreased AML cells’ ability to form colonies in vitro and tumors in vivo.
On the other hand, CHD4 depletion did not have detrimental effects on healthy bone marrow cells. The cells were no more sensitive to chemotherapy, and their growth was not affected.
Researchers reported these results in Blood.
“We are very encouraged by these findings,” said study author Gordon Ginder, MD, of Virginia Commonwealth University in Richmond.
“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.”
CHD4 is involved in silencing tumor suppressor genes in cancer cells. Recently, it has been shown to play a role in repairing DNA damage.
With their experiments, Dr Ginder and his colleagues found that CHD4 depletion severely restricted the ability of AML cells to develop colonies in soft agar models and establish tumors in mouse models.
In addition, blocking the production of CHD4 rendered AML cells more sensitive to daunorubicin and cytarabine, both in vitro and in vivo.
“This study builds on our team’s efforts to understand the molecular processes through which epigenetic regulators impact gene expression,” Dr Ginder said.
“Future studies will attempt to uncover the detailed mechanism through which CHD4 decreases the ability of AML cells to initiate leukemia and will look for potential ways to target this important protein. The fact that it functions as an enzyme suggests it may be druggable.”
