A New Approach to Treating Acute Lymphoblastic Leukemia

A team of researchers from the University of Zurich and the University Children’s Hospital Zurich has been scrutinizing the molecular causes of acute lymphoblastic leukemia (ALL). Their findings appeared in the journal Cancer Cell.

To conduct this research, they analyzed a protein typically found in ALL called TCF3-HLF and observed that the abnormal protein TCF3-HLF also activates a whole range of genes, and triggers the formation of malignant white blood cells. “Our research shows that the abnormal protein binds to almost 500 regulatory elements in the genetic material of the human leukemia cells, activating hundreds of genes by mistake,” explains Yun Huang, lead author of the study in a press release.

The researchers also discovered that the abnormal protein acts in combination with more than 100 other proteins around it, which facilitates the genes’ activation. “We investigated the function of the individual proteins in this genetic machinery and used this to identify key elements that could be targeted through therapy,” explains Huang.

One of the most essential proteins the researchers identified was EP300, a cofactor that boosts gene activation. The finding of a mouse-model experiment showed that EP300 could be a very promising target for therapy. In this investigation, the researchers used a substance called A-485, which is known to bind to EP300 and inhibit its activity. When A-485 was administered to mice carrying human leukemia cells, the malignant cells died off.

“It is therefore possible, in principle, to stop the fundamental driving force behind this leukemia directly and thus develop a targeted type of therapy,” says research group leader Jean-Pierre Bourquin. “The important thing now is to build a fuller picture of what goes wrong so that we can investigate the best possible way to combine specific modes of attack like this.” Given that other forms of leukemia are caused by similar mechanisms, it may also be possible to identify a common denominator for developing new drugs to combat cancer.