Researchers Identify Druggable Target in Acute Myeloid Leukemia Stem Cells

Researchers Identify Druggable Target in Acute Myeloid Leukemia Stem Cells

An international team of researchers has identified a druggable target in Acute Myeloid Leukemia (AML) stem cells which could serve as an effective treatment for the highly aggressive blood cancer.

AML is the second most common form of leukemia in adults and children. AML can affect people of all ages, but it is relatively rare in individuals under 45. The average age of diagnosis is 68. While treatment can be provided, it is not always effective. The problem is not targeting the cancer cells, which can be killed, but the cancer stem cells which are often left behind. They go on to form new cancer cells after treatment and the cancer returns. The five-year survival rate for individuals over 20 years of age is 24%. Each year, around 21,450 patients are diagnosed with AML in the United States and around 10,900 individuals die from the disease in the U.S. each year.

The research team, led by Peter MacCallum Cancer Centre’s Prof Mark Dawson and Dr. Laura MacPherson, has identified a way that the cancer stem cells can be targeted. Without the leukemia stem cells, once the cancer cells are eradicated the cancer should not return.

The researchers found a protein called HBO1 was essential for the survival of the cancer stem cells. They found that when the protein was eradicated in the lab and in a mouse AML model, the cells were no longer able to drive cancer growth. Once HBO1 was eradicated, the stem cells were no longer capable of dividing and turning into malignant forms. In many cases eradication of the protein led to cell death.

In order to develop a treatment, the researchers first needed to find out what part of the HBO1 protein was essential for maintaining its function in stem cells. Assisted by researchers in Melbourne, they developed a small molecule that was effective at suppressing the activity of HBO1. That small molecule is the first step in the process of creating a drug to target the protein in AML patients.

The researchers believe that their small molecule could well hold the key to treating AML and could significantly increase survival rates from this often-deadly form of leukemia.

The research is detailed in the paper – HBO1 is required for the maintenance of leukaemia stem cells – which was recently published in the journal Nature. DOI: 10.1038/s41586-019-1835-6

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