Putting a hex on leukaemia

Posted on Posted in Cancer, Medical News

Scientists have discovered that targeting a protein called Hhex could cure acute myeloid leukaemia (AML) in preclinical disease models and could also be a key target for new therapies for human leukaemia.

The research, led by Dr Ben Shields and Dr Matt McCormack from the Walter and Eliza Hall Institute, has been published in the journal Genes & Development.

AML is an aggressive blood cancer that appears suddenly, grows quickly and has a poor prognosis. Existing treatments are not cancer cell specific and unfortunately kill off healthy cells in the process; treated patients are thus prone to serious side effects. Furthermore, about three quarters of patients relapse after only a short period of treatment.

Dr Shields explained that AML cells switch off the controls that strictly manage cell growth and division. He said, “Every cell has control genes that are activated when a cell is stressed, such as in the early stages of cancer, and stop the damaged cell from reproducing.”

But while these control genes are still present in AML cells, they are switched off through a process called epigenetic modification — enabled by Hhex. “Hhex works by recruiting epigenetic factors to growth control genes, effectively silencing them,” Dr Shields said. “This allows the leukaemia cells to reproduce and accumulate more damage, contributing to the speed of AML progression.”

Now, the researchers have found that the loss of the protein effectively puts the handbrake on leukaemia cell growth and division. Dr McCormack said, “We showed blocking the Hhex protein could put the brakes on leukaemia growth and completely eliminate AML in preclinical models. This could be targeted by new drugs to treat AML in humans.”

Dr McCormack said drugs that inhibit epigenetic modification had been previously used to treat AML but caused significant toxicity because their targets were also required for normal blood cell function. Hhex, on the other hand, is overproduced and essential in leukaemia cells while being unneeded by healthy blood cells.

“Unlike the epigenetic factors targeted previously, Hhex only regulates a small number of genes and is dispensable for normal blood cells,” he said. “This gives us a rare opportunity to kill AML cells without causing many side effects.”

The researchers’ next goal, according to Dr McCormack, is to identify the regions of the Hhex protein that enable it to function.

“[This] will allow us to design much needed new drugs to treat AML,” he said.

Credit: http://www.lifescientist.com.au/

Picture Credit:  http://www.indianexpress.com

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