In a new research published in Cancer Cell, scientists wanted to fight the often fatal acute myeloid leukaemia (AML) by disabling parts of the machinery in cells called the transcriptional machinery that determines when genes are switched on and off. Researchers have developed a way of side-lining one of the most dangerous bad actors in leukaemia. The approach depends on throwing a molecular wrench into the gears of an important machine that sets genes into motion, enabling cancer cells to proliferate.

In tests in mice, the newly discovered method has resulted in what the researchers describe as the melting away of aggressive blood cancers while at the same time having no harmful impact on the function of normal cells.

Central players in this machinery are proteins called transcription factors, thousands of which are active in regulating genes across the chromosomes. The team sought to know how to target one of the most troublesome transcription factors, called MYB.

MYB is an oncogenic, or cancer-inducing, a transcription factor that enables cells to blow through the stop signs that normally prevent out-of-control growth. MYB is a dream target in cancer research since it is involved in so many cancers.

In leukaemia, MYB is special because by targeting MYB, the growth of AML can be stopped and can also be regressed. The researchers have discovered how to selectively take MYB out of the picture in leukaemia by throwing a molecular wrench into the mechanism that the transcription factor normally activates.

First, the team discovered that MYB activates gene expression by docking at a giant gene-co-activation protein called TFIID (pronounced TF-two-D). Next, they found a tiny weak spot on the massive protein.

This Achilles' heel, called TAF12, is a small, nub-like projection. The team then tricked MYB into binding to short protein fragments, or peptides, that are shaped exactly like the place on TAF12 where MYB binds when it is promoting leukaemia.

A major achievement in the study was generating the peptide, which acts like a decoy. Experiments in mice that model human AML showed that the peptide finds and binds MYB, preventing it from engaging the TFIID co-activator.

This resulted in mouse leukemias shrinking in size by some 80% without causing harm to healthy cells. While the peptide is not itself a drug, its action could be replicated by a drug. It is a concept we're now discussing with the pharmaceutical industry.

Associate Professor Christopher Vakoc said, “It is going to take lots of work before it can result in a medicine leukaemia patients might take. But we are excited about the new approach, because MYB is such an important player in many cancers and until now has eluded efforts to selectively target it."