Navigation Links
Researchers make critical leukemia stem cell discovery
Date:12/13/2010

Researchers at King's College London have discovered that leukaemic stem cells can be reversed to a pre-leukaemic stage by suppressing a protein called beta-catenin found in the blood.

They also found that advanced leukaemic stem cells that had become resistant to treatment could be 're-sensitised' to treatment by suppressing the same protein.

Professor Eric So, who led the study at the Department of Haematology at King's College London, says the findings, published today in the journal Cancer Cell, represent a 'critical step forward' in the search for more effective treatments for aggressive forms of leukaemia.

The role that beta-catenin plays in the development and drug-resistance of stem cells in acute leukaemia was previously unknown. This study, funded by the Association for International Cancer Research (AICR), Cancer Research UK and the Kay Kendall Leukaemia Fund, reveals its significance and highlights it as a potential therapeutic target that could allow selective eradication of leukaemic stem cells.

King's scientists looked at leukaemic stem cells found in types of leukaemia that involve mutations of the MLL gene. This accounts for around 70 per cent of infant leukaemias and 10 per cent of adult acute leukaemias. The prognosis for this type of leukaemia in children is not good only 50 per cent survive past two years after receiving standard anti-leukaemia treatment.

To understand how the disease develops, the King's team carried out a series of experiments to look at how pre-leukaemic stem cells (which do not always develop into leukaemia) are different to leukaemic stem cells, which sustain the disease and are likely to be responsible for relapse. They carried out studies in mice, in cultured human cells derived from cord blood, and on human leukaemic cells obtained from two leukaemia patients.

The studies in mice showed that pre-leukaemic cells developed into leukaemic stem cells and induced leukaemia, in part by activation of beta-catenin. But suppression of beta-catenin in leukaemic stem cells reduced leukaemic cell growth, delayed the onset of leukaemia and reversed the stem cells to a pre-leukaemic stage. Furthermore, when beta-catenin was completely inactivated in mice with pre-leukaemic cells, the mice did not develop leukaemia, even though they carried MLL gene mutations.

Researchers then wanted to see how suppression of the beta-catenin protein impaired human leukaemic cells. They found that suppression of the protein in MLL leukaemic cells again diminished their ability to proliferate and renew themselves (an essential part of how leukaemia develops). This confirmed the important role of beta-catenin in the human disease.

The study also revealed a previously unrecognized critical function of beta-catenin in mediating drug resistant properties of leukaemic stem cells. Leukaemic stem cells can become resistant to treatment in some cases but, crucially, this study showed that suppression of beta-catenin in human MLL leukaemic cells made them sensitive again.

Professor Eric So, who led the study at King's, said: 'These results are extremely exciting and represent a critical step forward in the search for more effective treatments for this devastating form of leukaemia. The findings provide compelling evidence that this protein could be exploited to develop an effective therapeutic target for this form of the disease.

'Most of the current anti-cancer therapies used to treat leukaemia attack healthy blood cells as well as cancerous ones. Interestingly, beta-catenin is not required for normal blood stem cells. So if we can specifically target beta-catenin in the bone marrow, we can have potentially a more effective and less toxic anti-leukaemia therapy that can efficiently eradicate leukaemic stem cells but spares healthy blood stem cells.

'Much more research needs to be done before we can adopt this approach in treating people with leukaemia, but the findings of this study do look promising. We will now investigate the mechanisms behind these molecular changes to find out why beta-catenin is so important in the development of MLL leukaemia, and if we can apply the principle to other types of leukaemia.'

Dr Mark Matfield, AICR's scientific co-ordinator said: 'The whole field of cancer stem cell research is relatively new, but this discovery has the potential to be one of the most useful in this rapidly-advancing area, because it shows us directly how a new treatment could be developed.'


'/>"/>

Contact: Emma Reynolds
emma.reynolds@kcl.ac.uk
44-207-848-4334
King's College London
Source:Eurekalert

Related medicine news :

1. Researchers map all the fragile sites of the yeast Saccharomyces cerevisiaes genome
2. UH Case Medical Center researchers publish promising findings for advanced cervical cancer
3. Researchers discover new way to kill pediatric brain tumors
4. Researchers Who Discovered First Genes for Stuttering will Present Findings to the National Stuttering Association
5. Researchers create drug to keep tumor growth switched off
6. Urine protein test might help diagnose kidney damage from lupus, UT Southwestern researchers find
7. GUMC researchers say flower power may reduce resistance to breast cancer drug tamoxifen
8. Clemson researchers develop hands-free texting application
9. Researchers find biomarkers in saliva for detection of early-stage pancreatic cancer
10. Researchers chart genomic map spanning over 2 dozen cancers
11. Researchers discover second protective role for tumor-suppressor
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:2/13/2016)... ... ... DDi , a Makro company, makes it to ... in eClinical Solutions. DDi has built its solution competency with a unique blend ... DDi provides smarter technology for Clinical Development, Regulatory and Enterprise domains by providing ...
(Date:2/12/2016)... , ... February 12, 2016 , ... ... devoted exclusively to funding innovative lymphoma research and serving the lymphoma community through ... over 250 members of South Florida’s philanthropic community at its 10th anniversary Fashion ...
(Date:2/12/2016)... ... 2016 , ... Coco Libre, the maker of coconut water beverages with a ... Lounge Event. Coco Libre will offer musicians and celebrities the company’s signature Organic Coconut ... invitation-only gifting suite, held this year at the W Hollywood Hotel, has become a ...
(Date:2/12/2016)... ... February 12, 2016 , ... Fisher House Foundation Chairman ... John J. Lee, Nevada Military Support Alliance president Scott Bensing, and Peggy Kearns Director, ... VA Southern Nevada Healthcare System. This will be the first Fisher House in ...
(Date:2/12/2016)... ... February 12, 2016 , ... Young ... area, celebrates the beginning of the latest charity campaign in their community enrichment ... art. Donations to this worthy cause are currently being accepted at: http://artexpressioninc.org/ ...
Breaking Medicine News(10 mins):
(Date:2/12/2016)... , Kalifornien, 12. Februar 2016  Sequent ... der Aufnahme von Patienten für eine Studie zur ... Aneurysmen („WEB") speziell für die Behandlung von rupturierten ... , MD, Leiter der Neuroradiologie an der Universitätsklinik ... und Hauptprüfarzt der CLARYS-Studie hat den ersten Patienten ...
(Date:2/12/2016)... , Feb. 12, 2016  Eli Lilly and Company ... Court decided the Alimta® (pemetrexed disodium) vitamin regimen patent would ... the UK, France , Italy ... to dilute the product only with dextrose solution.  ... 2015, the UK Court of Appeal held that Lilly,s patent ...
(Date:2/12/2016)... BUDAPEST , Ungarn, February 12, 2016 ... ein Medizintechnikunternehmen, das sich auf den ungedeckten ... gab heute positive Ergebnisse seines klinischen Forschungsprogramms ... und Asthma-Patienten beschäftigt, ergab Verbesserungen ihrer respiratorischen ... Indiso ltd , ein Medizintechnikunternehmen, das ...
Breaking Medicine Technology: