Eliminating a protein essential for leukaemia cell growth can stop the disease from progressing, scientists revealed.
The protein Hhex is produced in excess in patients with the disease – enabling cancerous cells to ‘grow uncontrollably’.
However, the protein isn’t needed by healthy blood cells, so removing it does not cause patients any harm, researchers noted.
And so, scientists from Walter and Eliza Hall Institute of Medical Research in Melbourne targeted Hhex in preclinical disease models.
They found they can put a ‘handbrake’ on acute myeloid leukaemia cell growth and division.
This finding could pave the way for new therapies for leukaemia, they said.
Eliminating a key protein necessary for acute myeloid leukaemia cell growth can stop the disease in its tracks, scientists revealed. The protein Hhex is overproduced in leukaemia and enables diseased cells to grow uncontrollably – but isn’t necessary for healthy blood cells, the new study found. Pictured, leukemia cells
Study co-author Dr Matt McCormack said: ‘Hhex is only essential for the leukaemic cells, meaning we could target and treat leukaemia without toxic effects on normal cells, avoiding many of the serious side-effects that come with standard cancer treatments.’
Acute myeloid leukaemia is an aggressive blood cancer that develops suddenly, grows quickly and has a poor prognosis.
Currently, AML treatments are associated with serious side-effects.
Nearly three-quarters of patients relapse after only a short period of treatment.
Furthermore, the disease carries a five-year survival rate of only 24 per cent.
Dr McCormack said: ‘There is an urgent need for new therapies to treat AML.
‘We showed blocking the Hhex protein could put the brakes on leukaemia growth and completely eliminate AML in preclinical models.
There is an urgent need for new therapies to treat [acute myeloid leukaemia]. We showed blocking the Hhex protein could put the brakes on leukaemia growth and completely eliminate AML in preclinical models
Dr Matt McCormack, of Walter and Eliza Hall Institute in Melbourne
‘This could be targeted by new drugs to treat AML in humans.’
Most existing AML treatments are not cancer cell-specific.
Thus, the therapies end up killing off healthy cells in the process as well.
During the study, the scientists found that AML cells switched off the controls that strictly manage cell growth and division.
Study co-author Dr Ben Shields said: ‘Every cell has control genes that are activated when a cell is stressed, such as the early stages of cancer, and stop the damaged cells from reproducing.’
Those control genes are still present in AML cells, but they switched off through a process called epigenetic modification.
Dr Shields said: ‘Hhex works by recruiting epigenetic factors to growth control genes, effectively silencing them.
‘This allows the leukaemia cells to reproduce and accumulate more damage, contributing to the speed of AML progression.’
Leukaemia treatments currently have adverse side effects – and can kill off healthy cells in the process. The scientists from Walter and Eliza Hall Institute (pictured) said their study could lead to new treatments
Drugs that inhibit epigenetic modification had previously been used to treat AML.
However, that caused ‘significant toxicity’ because their targets were also required for normal blood cell function.
Dr McCormack said: ‘Unlike the epigenetic factors targeted previously, Hhex only regulates a small number of genes and is dispensable for normal blood cells.
‘This gives us a rare opportunity to kill AML cells without causing many side effects.
‘We now hope to identify the critical regions of the Hhex protein that enable it to function, which will allow us to design much-needed new drugs to treat AML.’
The study was published in the journal Genes and Development.