Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Why Some Forms of Leukemia Only Affect Children

30.10.2019

Acute myeloid leukemia (AML) mainly affects children, with the prognosis often being poor despite several decades of research into more effective treatments. A new study led by researchers from the University of Basel and from Gustave Roussy Institute, Paris, explains why some forms of leukemia develop only in infants. The study also reveals potential new therapeutic targets, as the researchers report in the journal Cancer Discovery.

Over recent decades, research into pediatric cancer has intensified and treatments have improved, but the prognosis remains particularly unfavorable for young patients. Acute myeloid leukemia (AML) accounts for 15% of cases of leukemia diagnosed in children and adolescents. Overall survival at age five is around 60%, with relapse being the most common cause of mortality.


Fusion gene in tumor cells: Red signals show the ETO2 gene locus, green signals the GLIS2 locus and yellow signals the ETO2-GLIS2 fusion.

Chrystele Bilhou-Nabera & Nassera Abermil, Hôpital Saint Antoine, Paris.

Abnormal protein fusion

There are several subtypes of AML. One of the most aggressive types, which is linked to treatment resistance and a particularly unfavorable prognosis, is acute megakaryoblastic leukemia (AML-M7).

It was on this particular form of leukemia that the research teams of Prof. Dr. Jürg Schwaller (University Children’s Hospital Basel and Department of Biomedicine at the University of Basel) and Prof. Dr. Thomas Mercher (INSERM U1170 at Gustave Roussy Institute, Université Paris Saclay) focused their attention.

In 2012, the research team around Mercher found that AML-M7 frequently presents genetic alterations that lead to the expression of an abnormal protein resulting from the fusion of the two proteins normally independent in the cell.

Although this fusion – known as ETO2-GLIS2 – has been identified in 30% of AML-M7 cases, the researchers had been unable to explain this abnormality. Similarly, it was unclear why children with AML-M7 are on average under age two while older children (on average towards the age of 6) are usually diagnosed with other pediatric AML subtypes.

Targeted inhibition

To address these questions, the researchers developed a mouse model of AML-M7 to study the expression of ETO2-GLIS2 fusion. In this model, the researchers could first show that the activation of ETO2-GLIS2 fusion in fetal hematopoietic cells is sufficient to rapidly induce aggressive leukemia – which is very similar to AML-M7.

If, on the other hand, the fusion was activated in blood-forming cells of adult animals, this childhood leukemia did not occur, whereas other forms of AML developed much later. Moreover, by blocking ETO2-GLIS2 fusion in the in vivo model, researchers were able to bring tumor proliferation to a halt, with the abnormal blood cells once again able to differentiate into normal blood cells.

These findings suggest that this particular type of leukemia only occurs in infants because fetal hematopoietic cells – unlike adult ones – are more sensitive to certain genetic mutations such as ETO2-GLIS2 fusion. The study also shows that ETO2-GLIS2 fusion is the actual motor of this form of pediatric leukemia. The researchers will now try to directly inhibit the activity of this fusion in the tumor cells.

Wissenschaftliche Ansprechpartner:

Prof. Dr. Jürg Schwaller, Department of Biomedicine, University of Basel and University Children’s Hospital Basel, phone +41 61 265 35 17, email: j.schwaller@unibas.ch

Originalpublikation:

Cécile K. Lopez et al.
Ontogenic changes in hematopoietic hierarchy determine pediatric specificity and disease phenotype in fusion oncogene-driven myeloid leukemia
Cancer Discovery (2019), doi: 10.1158/2159-8290.CD-18-1463

https://cancerdiscovery.aacrjournals.org/content/early/2019/10/25/2159-8290.CD-1...

Iris Mickein | Universität Basel
Further information:
http://www.unibas.ch

Further reports about: AML blood cells hematopoietic leukemia myeloid leukemia

More articles from Life Sciences:

nachricht Researchers discover vaccine to strengthen the immune system of plants
24.01.2020 | Westfälische Wilhelms-Universität Münster

nachricht Brain-cell helpers powered by norepinephrine during fear-memory formation
24.01.2020 | RIKEN

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Integrate Micro Chips for electronic Skin

Researchers from Dresden and Osaka present the first fully integrated flexible electronics made of magnetic sensors and organic circuits which opens the path towards the development of electronic skin.

Human skin is a fascinating and multifunctional organ with unique properties originating from its flexible and compliant nature. It allows for interfacing with...

Im Focus: Dresden researchers discover resistance mechanism in aggressive cancer

Protease blocks guardian function against uncontrolled cell division

Researchers of the Carl Gustav Carus University Hospital Dresden at the National Center for Tumor Diseases Dresden (NCT/UCC), together with an international...

Im Focus: New roles found for Huntington's disease protein

Crucial role in synapse formation could be new avenue toward treatment

A Duke University research team has identified a new function of a gene called huntingtin, a mutation of which underlies the progressive neurodegenerative...

Im Focus: A new look at 'strange metals'

For years, a new synthesis method has been developed at TU Wien (Vienna) to unlock the secrets of "strange metals". Now a breakthrough has been achieved. The results have been published in "Science".

Superconductors allow electrical current to flow without any resistance - but only below a certain critical temperature. Many materials have to be cooled down...

Im Focus: Programmable nests for cells

KIT researchers develop novel composites of DNA, silica particles, and carbon nanotubes -- Properties can be tailored to various applications

Using DNA, smallest silica particles, and carbon nanotubes, researchers of Karlsruhe Institute of Technology (KIT) developed novel programmable materials....

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

11th Advanced Battery Power Conference, March 24-25, 2020 in Münster/Germany

16.01.2020 | Event News

Laser Colloquium Hydrogen LKH2: fast and reliable fuel cell manufacturing

15.01.2020 | Event News

„Advanced Battery Power“- Conference, Contributions are welcome!

07.01.2020 | Event News

 
Latest News

Researchers discover vaccine to strengthen the immune system of plants

24.01.2020 | Life Sciences

Brain-cell helpers powered by norepinephrine during fear-memory formation

24.01.2020 | Life Sciences

Engineered capillaries model traffic in tiny blood vessels

24.01.2020 | Life Sciences

VideoLinks
Science & Research
Overview of more VideoLinks >>>