December 10 (Beijing time) reported that at the 54th Annual American Blood Association Annual Meeting and Expo held in Atlanta on December 9, the Temple University School of Medicine reported that they were studying the treatment of chronic myeloid leukemia (CML) Progress. They devised a method to shut down the activity of CML stem cells to stop the further development of the disease. The researchers pointed out that the discovery is expected to bring new personalized therapies that overcome cancer stem cell resistance.
In CML, the genes ABL1 and BCR in bone marrow stem cells fuse together to produce an enzyme called BCR-ABL1, which produces too many white blood cells under its drive. Although imatinib is a relatively successful drug in treatment, patients are always at risk of relapse. Thomas Skosky, senior author of the paper and professor of microbiology and immunology at Temple University School of Medicine, explained that leukemia has a small bank of stem cells to fight against treatment. The remaining leukemia stem cells will accumulate a large number of deadly DNA mutations and can effectively self Repairing, thereby burying fatal hidden dangers in the DNA, eventually leading to a worsening of the condition.
To this end, the research team used a method that would not damage normal cells to attack the path of DNA repair by leukemia stem cells, and the repair mechanism of normal cells is different from leukemia cells. They conducted a series of experiments with mice, and showed that targeting a special protein, RAD52, can suppress the self-repair process of leukemia stem cells. "We hope this method can eradicate leukemia stem cells and cure patients with chronic myeloid leukemia." Skoski said.
"Our earlier research also found that the RAD52 gene is a key factor in the development of leukemia." Kimberley Clem, the first author of the paper and a postdoctoral fellow in microbiology and immunology at the school, said that when mouse bone marrow cells lack RAD52, CML will stop Development, which shows that CML depends on RAD52 to achieve its own DNA repair.
One of the most common DNA damage is "double-strand break". When the RAD52 protein is mutated, it can no longer bind to DNA to repair the break. The researchers added an "aptamer" to BCR-ABL1-positive bone marrow cells and found that RAD52 was prevented from binding to DNA. Leukemia bone marrow cells accumulated too much double-strand breaks and eventually died, while aptamers were normal cells. Then there is no effect.
Clem said: "In this way, a small molecule inhibitor may eventually be produced to target leukemia cells from its tumorigenic roots." Skoski added that the method is also expected to be extended to other cancers.
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