Navigation Links
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 light on the function of Pax5, which was one of about 100 genes known to 'suppress' human tumours. "When these tumour suppressor genes are inactivated by changes to the DNA, cancers start to develop," Dr Dickins said.

"This work shows how inactivating the tumour suppressor gene Pax5 contributes to B-ALL development and how leukaemia cells become 'addicted' to low Pax5 levels to continue proliferating. Even though the B-ALL cells have multiple genetic mutations, simply reactivating Pax5 causes tumour cells to resume normal development and lose their cancerous properties."

Dr Dickins said forcing B-ALL cells to resume their normal development could provide a new strategy for treating leukaemia. "While B-ALL has a relatively good prognosis compared with other cancers, current treatments can last years and have major side-effects. By understanding how specific genetic changes drive B-ALL, it may be possible to develop more specific treatments that act faster with fewer side-effects."

However Dr Dickins said that genes that are lost in tumour cells are not traditionally drug targets. "It is very difficult to develop drugs that restore the function of genes that are lost during cancer development," Dr Dickins said. "However by understanding the mechanisms by which Pax5 loss causes leukaemia, we can begin to look at ways of developing drugs that could have the same effect as restoring Pax5 function."

The genetic switch technology used to study Pax5 could also be used to understand 'tumour suppressor' genes in other cancers, he said.


'/>"/>
Contact: Liz Williams
williams@wehi.edu.au
61-428-034-089
Walter and Eliza Hall Institute
Source:Eurekalert  

Related medicine news :

1. Tugging on the malignant switch
2. Team finds on-off switch to burning stored fat
3. Cancers potential on-off switch
4. Vascular simulation research reveals new mechanism that switches in disease
5. Our brain has switch board to guide behavior in response to external stimuli
6. Short circuit in molecular switch intensifies pain
7. Bariatric Surgeon in Mexico Dr. Jose A. Castaneda Introduces New Duodenal Switch With Single Anastomosis
8. Supercomputers help ORNL researchers identify key molecular switch that controls cell behavior
9. NetPlus® Leads in Security as the only Telecommunications Management System Certified by JITC on all Unified Communications and Legacy Switches
10. Victoria Staley, AMTC Aluma, Gets Lead Role in Switching Lanes Coming Out in 2014 and in Current Film Prisoners
11. X-ES Announces Fully Packaged Rugged Ethernet Switching and Routing Solutions
Post Your Comments:
*Name:
*Comment:
*Email:
Related Image:
Gene 'switch' reverses cancer in common childhood leukaemia
(Date:6/24/2016)... ... 24, 2016 , ... People across the U.S. are sharpening their pencils and ... essay contest in which patients and their families pay tribute to a genetic counselor ... National Society of Genetic Counselors (NSGC) Annual Education Conference (AEC) this September. , ...
(Date:6/24/2016)... ... 24, 2016 , ... The Haute Beauty Network, affiliated with ... as a prominent plastic surgeon and the network’s newest partner. , Dr. ... handsome men, look naturally attractive. Plastic surgery should be invisible.” He stands by ...
(Date:6/24/2016)... ... June 24, 2016 , ... Strategic Capital Partners, LLC ... by obtaining investment capital for emerging technology companies. SCP has delivered investment ... resulted in more than a million dollars of capital investment for five companies. ...
(Date:6/24/2016)... ... June 24, 2016 , ... Venture Construction Group (VCG) ... held on June 20th at the Woodmont Country Club at 1201 Rockville Pike, ... organization dedicated to helping service members that have been wounded in battle and their ...
(Date:6/24/2016)... ... June 24, 2016 , ... Advanced Plastic Surgery Institute ( ... as its official Medspa Sponsor. Dr. Josh Olson, a board-certified plastic surgeon, owns ... Dr. Olson says the decision to support the pageant in an official capacity ...
Breaking Medicine News(10 mins):
(Date:6/24/2016)... , June 24, 2016 ... of the "Structural Electronics 2015-2025: Applications, Technologies, ... In-Mold Electronics, Smart Skin, ... Photovoltaics Structural electronics involves electronic ... load-bearing, protective structures, replacing dumb structures such as ...
(Date:6/24/2016)... CLEMENTE, Calif. , June 24, 2016  American Respiratory Labs ... company, is now able to perform sophisticated lung assessments in patients, ... Technologies , Inc. Patients are no longer limited ... ndd,s EasyOne PRO ® , ARL patients like Jeanne R. of ... done in the comfort of her own home. ...
(Date:6/24/2016)... June 24, 2016   Pulmatrix, Inc ., (NASDAQ: ... innovative inhaled drugs, announced today that it was added ... reconstituted its comprehensive set of U.S. and global ... is an important milestone for Pulmatrix," said Chief Executive ... awareness of our progress in developing drugs for crucial ...
Breaking Medicine Technology: