MURDOCH University biomedical scientist Dr Wayne Greene hopes to solve one of medical science’s most baffling mysteries - how to combat childhood leukaemia.

According to Dr Greene, although we are now able to treat childhood lymphoblastic leukaemia (or cancer of the lymphocytes) reasonably successfully, researchers still have a long way to go before it is completely curable.

Dr Greene, who is researching the disease at Murdoch University’s Division of Veterinary and Biomedical Sciences, said leukaemia was the major type of cancer found in children.

Working in close collaboration with Dr Ursula Kees at the TVW Telethon Institute for Child Health Research at Princess Margaret Hospital for Children, the research has been boosted by a recent National Health and Medical Research Council (NH&MRC) grant for $367,000 given over three years.

“Fortunately, childhood leukaemia is a rare disorder occurring in only one in several thousand children,” said Dr Greene.

“What makes it so devastating however, is that it primarily occurs in young children. Thus its impact on victims can be considerable in terms of years of life lost.”

He said up to fifty per cent of all childhood cancers occurred in the lymphoid cells or lymphocytes.

“These lymphoid cells are central to the development of the immune system,” said Dr Greene.

“They are also the only cells where the DNA blueprint is deliberately tampered with. This is somewhat risky - but also necessary - as it enables the body to generate the required range of T-cell receptors (TCRs) and antibodies to help fight disease.”

He said problems could occur, however, when the rearranging process, involving the breakage and rejoining of the DNA, went wrong.

“It is relatively rare but can happen,” said Dr Greene.

“In the case of T-cells, instead of rearranging the TCR genes themselves, the chromosome harbouring the TCR genes can abnormally join up with a different chromosome.

“This chance event is known as a chromosomal translocation that indelibly changes the cell’s fate.”

Dr Greene said about 50 per cent of T-lymphocyte tumours in children had such a translocation.

“This results in a critical gene being switched on that should not have been,” he said.

“Much of the research in the past 15 or 20 years has focused on particular genes affected by these chromosomal translocations,” said Dr Greene.

“Several genes have already been discovered and these have largely turned out to be ‘master’ or ‘transcription factor’ genes that were wrongly switched on.

“What we really need now is an understanding of how these transcription factors convert an ostensibly normal cell into a cancerous one, since transcription factors control the activity of other genes.”

He said research in this area had increasingly focused on so-called ‘subordinate genes’.

He said since it was impossible for researchers to study all of the transcription factors, it made sense to concentrate on one in particular, in this case the transcription factor HOX11.

“HOX11 belongs to a family of factors which specify the body plan,” said Dr Greene.

“This gene family is extremely important, being found in flies through to humans and thus forming an integral part of our evolution and morphology.”

He said HOX11’s specific role appeared to be in the development of the spleen, and without it there would be no spleen.

“In T-cell leukaemia where HOX11 is wrongly activated, we are working to find out exactly which subordinate genes cause these cells to become cancerous,” he said.

Dr Greene’s previous research took place in England in the mid-1990s, where he made his first major breakthrough with the discovery of a gene controlled by HOX11.

“This gene specifies an enzyme involved in the manufacture of an extremely important hormone called retinoic acid (an acid form of vitamin A),” he said.

As a postdoctorate student on a CJ Martin Fellowship from the NH&MRC, Dr Greene spent nearly three years at the prestigious MRC Laboratory of Molecular Biology in Cambridge under the auspices of eminent leukaemia expert Professor Terence Rabbitts.

Dr Greene returned to Perth in 1997 to continue his research into childhood leukaemia.