Low doses of amycin may overcome leukemia resistance

a new study published online April 20 in Nature Cell Biology, Researchers in China and the United States report on a new approach that could overcome leukemia resistance: the use of low-dose, chemotherapy drug ammoxin, widely used to treat multiple cancers.
traditional chemotherapy or radiation therapy for cancer, although it has some effect in the early stages of treatment, but the resulting resistance often leads to the recurrence of cancer. In recent years, anti-immunotherapy gene therapy (immunotherapy) has become a new way to treat cancer, but immunotherapy has shown good results only in limited types of cancer, and a large proportion of patients are still relapsing after immunotherapy. Therefore, the basic mechanism of resistance, including immune escape, is the fundamental problem that needs to be solved urgently.
, the researchers hypothesized that Akt phosphorylation, which inhibits β-serial protein, reduced the activity of the former and inhibited leukemia. To test this hypothesis, researchers at the Stewarts Institute of Medicine, the University of Kansas and Tsinghua University in China conducted high-volume screening of chemical libraries approved by the U.S. Food and Drug Administration and identified 24 pilot compounds. It was found that the widely used chemotherapy drug amycin specifically inhibited the interaction between Akt and β-serial proteins at low doses.
researchers used low-dose amycin with the clinically used chemotherapy drug nairabin to treat double-mutant mice. They observed that chemotherapy was effective in eliminating the majority of leukemia cells, but induced the amplification of a small number of leukemia stem cells. In contrast, low doses of amycin had no effect on leukemia cells, but reduced leukemia stem cells. The combination of low-dose amycin and nairabin worked best. To further confirm the inhibitory effects, the researchers collaborated in a small clinical trial to test the response of 10 to 20 patients with acute myeloid leukemia who had become resistant to chemotherapy to erythromycin. The results showed that 50% of patients with acute myeloid leukemia who were already resistant to chemotherapy responded to low doses of erythromycin and significantly reduced the number of leukemia stem cells.
study also found that the inhibition of low-dose amycin on leukemia stem cells depends on T cells that fight cancer by expressing CD8. As a result, new treatments target not only leukemia stem cells directly, but also expose them to activated immune responses. (Source: Tang Erdu, China Science Journal)
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