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Gene 'switch' reverses cancer in common childhood leukaemia
Date:6/17/2014

Melbourne researchers have shown a type of leukaemia can be successfully 'reversed' by coaxing the cancer cells back into normal development.

The discovery was made using a model of B-progenitor acute lymphoblastic leukaemia (B-ALL), the most common cancer affecting children.

Researchers from the Walter and Eliza Hall Institute showed that switching off a gene called Pax5 could cause cancer in a model of B-ALL, while restoring its function could 'cure' the disease.

Institute researchers Dr Ross Dickins and Ms Grace Liu led the study with institute colleagues and collaborators in Vienna. The study was published today in the journal Genes & Development.

Ms Liu said the team used a newly developed 'genetic switch' technology to inhibit then reactivate Pax5 in the leukaemia model.

"Along with other genetic changes, deactivating Pax5 drives normal blood cells to turn into leukaemia cells, which has been shown before," Ms Liu said. "However we showed for the first time that reactivating Pax5 enabled the cells to resume their normal development and lose their cancer-like qualities, effectively curing the leukaemia. What was intriguing for us was that simply restoring Pax5 was enough to normalise these cancer cells, despite the other genetic changes."

In leukaemia, immature white blood cells replicate abnormally and build up in the bone marrow, interfering with production of normal blood cells.

Ms Liu said Pax5 was a gene frequently 'lost' in childhood B-ALL. "Pax5 is essential for normal development of a type of white blood cells called B cells," she said. "When Pax5 function is compromised, developing B cells can get trapped in an immature state and become cancerous. We have shown that restoring Pax5 function, even in cells that have already become cancerous, removes this 'block', and enables the cells to develop into normal white blood cells."

Dr Dickins said the research shed l
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Contact: Liz Williams
williams@wehi.edu.au
61-428-034-089
Walter and Eliza Hall Institute
Source:Eurekalert  

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