Experiments on mice offer hope for effective leukaemia treatment
Scientists have discovered a weak point in leukaemia stem cells which it appears could be utilised in effective treatment of acute myeloid leukaemia.
Around 200 Danes contract acute myeloid leukaemia (AML) each year. The disease primarily affects the elderly and offers a bleak prognosis. According to the Danish Cancer Society, only one in five of the adult patients remain alive five years after the diagnosis of this type of acute leukaemia. The poor survival rate is primarily due to the fact that the majority of patients experience relapses following chemotherapy.
The researchers’ hypothesis is that the disease returns in the patients due to the leukaemia stem cells in the body, as it is often not possible to remove them using chemotherapy. The cancer stem cells comprise less than one per cent of the total cancer cells, but they are more difficult to defeat than the other cancer cells. They can both lead to relapses and can also spread the cancer.
But researchers from Aarhus University and Goethe University Frankfurt am Main have now found a weak point with the stem cells which can quite possibly be used in the treatment of AML. The results have been published in the world's most cited scientific journal on cancer, Cancer Research.
Anti-inflammatory drugs defeat leukaemia stem cells
They have discovered an enzyme that has turned out to play an important role in ensuring that leukaemia stem cells can survive. The enzyme, named 5-lipoxygenase, is already known from e.g. asthma, where it causes bouts of asthma. Experiments with anti-inflammatory drugs on mice with acute myeloid leukaemia have shown that the cancer stem cells ability to develop leukaemia disappeared. The drugs contain so-called inhibitors which inhibit the enzyme’s activity.
"The results give us cause to hope that we can use the inhibitors to reduce the frequency of the relapses which we often see among patients following chemotherapy," says Thorsten Jürgen Maier, who is associate professor at Aarhus University and one of the researchers behind the experiments.
The cancer is often even more aggressive if it returns following chemotherapy. At the same time, patients are often weakened after chemotherapy. This is why it is crucial to avoid relapses if the prognosis is to be improved.
Need to be tested on humans
The new offensive strategy now needs to be investigated in more detail.
"These results form the basis for a possible use of the 5-lipoxygenase inhibitors as stem cell therapy for a sustainable cure for acute myeloid leukaemia. But this must firstly be studied further in pre-clinical and clinical studies in humans," explains medical doctor Martin Ruthardt from University Hospital Frankfurt .
First of all, the molecular mechanism must be mapped.
"We are now in the process of examining the molecular mechanism in more detail in order to find out how the inhibitors precisely work on the leukaemia stem cells. We very much hope that our results will be of benefit for leukaemia patients," adds Thorsten Jürgen Maier.
It may, however, take several years before the discovery can benefit patients. Development of medicine can take ten years from the point where scientists have a research result until this has been converted into an approved product.
Further information
Read the scientific article ”5-lipoxygenase is a candidate target for therapeutic management of stem cell-like cells in acute myeloid leukemia” in Cancer Research
Facts about acute leukaemia
- Also called cancer of the blood, it starts from the white blood cells in the bone marrow.
- There are two types of the disease: the most common is acute myeloid leukaemia (AML), which mostly occurs in adults. Acute lymphocytic leukaemia (ALL) is more rare and is seen mostly in children.
- In Denmark there are approx. 200 new cases of AML annually and approx. 50 cases of ALL.
- The cause of acute leukaemia is rarely known. It is only possible to find a triggering factor in approx. five per cent of patients with acute leukaemia.
- The disease can only be cured with intensive chemotherapy and possibly a bone marrow transplant.
Source: The Danish Cancer Society
Further information
Associate Professor Thorsten Jürgen Maier
Aarhus University, Department of Biomedicine
Direct tel.: +45 8716 7681
maier@biomed.au.dk