Targeting Gfi1 protein may enhance leukemia treatment
Removing the Gfi1 protein from acute lymphoblastic leukemia (ALL) cells weakened and destroyed the cells in mice, researchers discovered. This action should make leukemia more susceptible to chemotherapy and radiation therapy.
As they reported in Cancer Cell (2013;23:200-214), H. Leighton Grimes, PhD, of Cincinnati Children's Hospital Medical Center in Cincinnati, Ohio, and colleagues found that leukemic cells depend on growth factor independence 1, or Gfi1, for survival. ALL relies on Gfi1 to escape the tumor-suppressing capabilities of another protein, p53. p53 normally initiates DNA repair that involves apoptosis, or programmed cell death, of cancer cells, but Gfi1 restricts p53 activity.
When Grimes and fellow researchers removed Gfi1 in lymphoid tumors in mice, the leukemia regressed through p53-induced apoptosis. The investigators then removed Gfi1 from human T-cell ALL cells implanted into mice. Gfi1 inhibition again stopped the progression of leukemia in the mice, without any harmful effects.
“Chemo and radiation therapies are very nonspecific and can be toxic to patients,” pointed out Grimes in a statement issued by Cincinnati Children's Hospital Medical Center. “Our findings suggest that combining the inhibition of Gfi1 with these treatments may allow the use of lower cytotoxic doses and directly benefit patients.”
The investigators will continue their research to determine whether these results will translate to human patients.