Research published in Nature Communications suggests that mutations in the ZBTB7A gene are associated with t(8;21)-rearranged acute myeloid leukemia (AML).
Investigators believe these mutations may be one of the “missing links” in RUNX1/RUNX1T1-driven leukemogenesis.
The team analyzed samples from 56 patients with t(8;21)-rearranged AML and identified recurring ZBTB7A mutations in 23% of those samples.
This included missense and truncating mutations that resulted in alteration or loss of the C-terminal zinc-finger domain of ZBTB7A.
The investigators noted that the transcription factor ZBTB7A is important for hematopoietic lineage fate decisions and for the regulation of glycolysis.
So the team was not surprised to find that ZBTB7A mutations boosted the energy metabolism in leukemia cells.
“In healthy cells, the active ZBTB7A gene acts like a parking brake on metabolism,” said study author Philipp Greif, MD, of Ludwig-Maximilians-Universität München in Munich, Germany.
“If the gene is defective, cancer cells get more energy to use for proliferation.”
Dr Greif and his colleagues also found they could reduce the growth rate of AML cells by increasing levels of active ZBTB7A.
And the team observed an indication of ZBTB7A’s growth-inhibiting effects in the clinic. Leukemia patients with higher levels of ZBTB7A expression had significantly better chances of survival than patients in whom the gene was hardly active or not active at all.
Now, the investigators plan to explore whether ZBTB7A expression can be used to customize therapies for individual patients. They also believe their discovery is a promising starting point for developing new approaches to treat AML.
“It might be possible to use specially modified glucose molecules to block the energy production process in AML cells,” said study author Luise Hartmann, of Ludwig-Maximilians-Universität München.
“Initial clinical trials in other cancers have already shown that these agents are well-tolerated by patients.”
