HKU Faculty of Medicine Study Found Promising Novel Therapeutic to Treat Deadly Blood Cancer

HKU Faculty of Medicine Study Found Promising Novel Therapeutic to Treat Deadly Blood Cancer
A team from the Faculty of Medicine at the University of Hong Kong has identified that PLK4 can be used as a new therapeutic to treat acute myeloid leukemia (AML) caused by TP53 gene mutations. (Courtesy of HKUMed)
By Yi Yang,
1/6/2024
Updated:
1/6/2024
0:00

A research team from the Faculty of Medicine at the University of Hong Kong (HKUMed) has identified a gene called polo-like kinase 4 (PLK4) that can be used as a new therapeutic to treat acute myeloid leukemia (AML), a fatal disease caused by TP53 gene mutations.

The research team is led by Professor Anskar Leung Yu-hung, Chair Professor of Hematology, Department of Medicine, School of Clinical Medicine, HKUMed. The team pointed out that AML is a blood cancer caused by genetic mutations in bone marrow cells. Its symptoms include fever, abnormal bleeding, and infection. If the patient does not receive timely treatment, it may deteriorate rapidly and could be fatal.

Traditional treatment options include high-dose chemotherapy and bone marrow transplant, with an overall success rate of only 40 percent of patients who do recover and enjoy long-term survival. However, in any case, conventional therapies do not perform well for AML subtypes, and there are currently no effective treatment options available for AML subtypes in the medical profession.

Earlier, the team conducted research and proceeded with a comprehensive analysis of gene expression against the drug response of different AML subtypes. It was found that the gene PLK4 is particularly active in TP53 (a tumor suppressor gene) mutated AML. TP53 mutated AML is resistant to chemotherapy yet highly vulnerable to prolonged PLK4 inhibition. However, PLK4 inhibition can also induce DNA damage, cell aging, and abnormal cell division.

The team also discovered that the combined effects of histone modifications and polyploidy do activate the cGAS-STING pathway, which triggers the immune system, and they have consistently observed such phenomenon through experiments in both the laboratory setting and animal models. They also found that the combined use of PLK4 inhibitors and CD47 monoclonal antibodies could enhance the macrophages killing capacity and help reduce the impact of leukemia, resulting in prolonged animal survival.

The team pointed out that the study has demonstrated the therapeutic effect of PLK4 inhibition on TP53-mutated AML. Subsequent clinical trials will be launched at the Hematology Division of Queen Mary Hospital in Hong Kong to evaluate the efficacy of PLK4 inhibitors in AML patients.

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