Pediatric cancers: Why some forms of leukemia only affect children

October 29, 2019

Each year, 2,500 pediatric cancers are diagnosed in France, with one third of cases concerning leukemia - commonly known as blood cancer. Over recent decades, research into pediatric cancer has intensified and treatments have improved, but the prognosis remains particularly unfavorable for these young patients.

Acute myeloid leukemia (AML) accounts for 15% of cases of leukemia diagnosed in children and adolescents. Overall survival at 5 years is around 60%, with relapse being the most common cause of mortality.

Abnormal protein fusion

There are several subtypes of AML. One of the most aggressive, which is linked to treatment resistance and a particularly unfavorable prognosis, is acute megakaryoblastic leukemia (AML-M7). In their new study published in Cancer Discovery, the team focused their efforts specifically on this type of acute myeloid leukemia."

The scientists obtained samples from young patients with AML-M7. In 2012, their analysis of these samples had already revealed AML-M7 to frequently present genetic alterations that lead to the expression of an abnormal protein resulting from the fusion of the two proteins normally independent in the cell. At that time, although this fusion - known as ETO2-GLIS2 - had been identified in 30% of AML-M7 cases, the researchers could not explain its mechanism of action.

They also wanted to understand why AML-M7 is diagnosed in children who are on average a lot younger (under 2 years of age) than those diagnosed with the other pediatric AML subtypes (on average towards the age of 6).

"One of the objectives of our new study was to look at the mechanism of action of the ETO2-GLIS2 fusion, and to better elucidate its consequences. We wanted to answer two major questions, with the first being why this disease is specific to children - since the fusion is not found in adults, and then what the potential therapeutic avenues could be", explains Thomas Mercher.

This involved the researchers analyzing the characteristics of human leukemia cells and developing a mouse model to study the consequences of the ETO2-GLIS2 fusion.

Towards new therapeutic avenues

In this model, the researchers showed that this fusion is sufficient in order to rapidly induce aggressive leukemia, if it is activated in fetal hematopoietic cells. However, there is little to link its activation in adult cells with the development of leukemia. Moreover, blocking the ETO2-GLIS2 fusion in the in vivo model brings tumor proliferation to a halt, with the abnormal blood cells once again able to differentiate into normal blood cells.

These findings suggest that some forms of leukemia develop specifically in children because the properties of the fetal cells differ from those of adult cells.

Findings which also make it possible to propose new target mechanisms in fetal cells and pediatric leukemia in order to improve treatments for these patients. "We now want to understand exactly how this fusion works. Targeting it in order to directly inhibit it with molecules that could be used in patients is not something we are able to do at present, so instead we will identify and try to target the surrounding proteins that are important for it to function", concludes Thomas Mercher.
-end-


INSERM (Institut national de la santé et de la recherche médicale)

Related Leukemia Articles from Brightsurf:

New therapeutic approach against leukemia
Using an RNA molecule complex, researchers can prevent retention of cancer stem cell in their tumor supporting niche

Nanoparticle for overcoming leukemia treatment resistance
One of the largest problems with cancer treatment is the development of resistance to anticancer therapies.

Key gene in leukemia discovered
Acute myeloid leukemia (AML) is one of the most common forms of blood cancer among adults and is associated with a low survival rate, and leads to the inhibition of normal blood formation.

Vitamin B6, leukemia's deadly addiction
Researchers from CSHL and Memorial Sloan Kettering Cancer Center have discovered how Acute Myeloid Leukemia is addicted to vitamin B6.

Artificial intelligence tracks down leukemia
Artificial intelligence can detect one of the most common forms of blood cancer - acute myeloid leukemia -- with high reliability.

Milestone reached in new leukemia drug
Using a chemical compound called YKL-05-099, a team of cancer researchers from CSHL and the Dana Farber Institute was able to target the Salt-Inducible Kinase 3 (SIK3) pathway and extend survival in mice with MLL leukemia.

The drug combination effective against bovine leukemia
Scientists have succeeded in reducing levels of the bovine leukemia virus (BLV) in cows with severe infections by combining an immune checkpoint inhibitor and an enzyme inhibitor.

Towards a safer treatment for leukemia
An international team of researchers at VIB-KU Leuven, Belgium, the UK Dementia Institute and the Children's Cancer Institute, Australia, have found a safer treatment for a specific type of leukemia.

Research paves way for new source for leukemia drug
Chemistry researchers have patented a method for making anti-leukemia compounds that until now have only been available via an Asian tree that produces them.

An atlas of an aggressive leukemia
A team of researchers led by Bradley Bernstein at the Ludwig Center at Harvard has used single-cell technologies and machine learning to create a detailed 'atlas of cell states' for acute myeloid leukemia (AML) that could help improve treatment of the aggressive cancer.

Read More: Leukemia News and Leukemia Current Events
Brightsurf.com is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to Amazon.com.