Screening for patients with leukemia anticancer drugs ineffective gene

Researchers in Korea have found a gene that determines the therapeutic effect of anticancer drugs used to treat leukemia. The research team of Korea Advanced Institute of Science and Technology (KAIST), Professor Yusik Kim of the Department of Chemical Engineering and Professor Junsik Hong of the Blood Cancer Center at Seoul National University Hospital, announced on the 7th that the mechanism of action of decitabine, an anticancer chemotherapy drug for leukemia, has been identified.


Decitabine is an anticancer drug used in the treatment of acute myelogenous leukemia (AML) and myelodysplastic syndrome (MDS). It triggers an immune response that kills cancer cells by removing the methyl group (-CH₃) present in deoxyribonucleic acid (DNA) in the human body.


In cancer cells, more DNA methylation (epigenetic change caused by attaching methyl groups to DNA) occurs in cancer cells than in normal cells. The higher the methylation level, the greater the tendency to inhibit transcription (the process of synthesizing RNA, which is a copy of DNA) do.


When decitabine is treated in cancer cells, the transcription process is activated due to demethylation, resulting in numerous ribonucleic acids (RNA). Among them, double-helix RNA (dsRNA) plays a role in removing cancer cells. Originally, dsRNA is produced in virus-infected cells, but it works on the principle that human cells recognize dsRNA generated in the body as foreign substances and activate immunity.


The research team analyzed dsRNA-binding proteins that interact with dsRNA, noting that many of the patients who received decitabine were not effective. As a result, it was revealed for the first time that the'Staufen1' gene, which directly binds to dsRNA, plays an important role in the action of decitabine.


In cells in which stauffen1 expression was suppressed, dsRNA was rapidly removed and no immune response occurred, and accordingly, death of cancer cells was not observed.


Another type of demethylation agent, azacytidine, was administered to 46 patients with acute myelogenous leukemia and myelodysplastic syndrome and found that the expression of staufen 1 was significantly reduced in the group without treatment effect.


Professor Kim Yoo-sik of the Department of Biochemical Engineering at KAIST said, by using the gene found this time as a biomarker (a biomarker that diagnoses the progression of the disease), the effects of DNA demethylation agents such as decitabine and azacytidine can be predicted. We will dramatically reduce the cost and time of treatment through customized cancer treatment.


The results of this study were published on the 30th of last month in the International Journal of the National Academy of Sciences (PNAS).

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