Scientists uncover basis for drug resistance in common childhood cancer
US scientists say they have worked out why acute lymphoblastic leukaemia (ALL) - the most common form of childhood cancer - can come back after treatment.
A research team at the University of California, San Francisco (UCSF), discovered that a protein called BCL6 helps to protect ALL cells against treatment with tyrosine kinase inhibitor (TKI) drugs such as imatinib (Glivec).
Although these drugs have changed the outlook for children and adults in recent years, in some cases treatment stops working and the cancer returns. This is thought to happen because TKI drugs don't destroy the leukaemia stem cells that can 'refuel' the disease.
The researchers, whose findings are published in the journal Nature, looked at 22,000 genes in ALL cells to see whether any were switched on or off when treated with TKI drugs.
They noticed that levels of the BCL6 protein rose significantly following treatment. BCL6 was already known to be active in other cancers, such as lymphoma, but this is the first study to link it to leukaemia.
Further experiments revealed that BCL6 was helping to keep cancer cells alive following TKI treatment by switching off a 'suicide' gene called p53, which normally causes faulty or cancerous cells to die. In particular, BCL6 helps to preserve the leukaemia stem cells that can 'regrow' the cancer.
The researchers then showed that by blocking the activity of BCL6 with an experimental drug in mice with leukaemia, they were able to significantly increase the effectiveness of imatinib treatment and improve survival. They saw the same results when they combined the BCL6-blocking drug with nilotinib, a more potent TKI drug.
This research is only at an early stage, but it suggests that BCL6 may provide a target for the development of new therapies that boost the effectiveness of treatment for ALL and improve long-term survival.
Senior author Dr Markus Muschen, professor of laboratory medicine at UCSF, said that BCL6 acts "like an emergency mechanism, whereby tumour cells try to evade drug treatment".
Dr Kat Arney, science information manager at Cancer Research UK, said: "These new results are exciting and could make a significant impact on the treatment of this type of leukaemia in the future. Although this research is only in the lab at the moment, we hope it will move quickly towards clinical trials in patients."