From The Labs

A potential Achilles heel of pediatric acute myeloid leukemia

Acute myeloid leukemia (AML) is a type of blood cancer that makes it hard for the body to fight infection. Dr. Joanna Yi, assistant professor of pediatrics-oncology at Baylor College of Medicine and Texas Children’s Hospital, studies AML in children. In this study, she and her colleagues focused on finding more effective and less toxic treatments for this devastating disease.

Microscopy view of acute myeloid leulemia. National Cancer Institute.

Yi and colleagues’ approach involved identifying molecular drivers of pediatric AML that were specifically expressed in leukemia cells and absent in normal cells.

“This would increase the chances of developing a more effective treatment for AML that would specifically attack the leukemia cells while having no or minimal effects on normal cells in the body,” Yi said.

Dr. Joanna Yi

In general, Yi explained, pediatric cancers are genomically quiet, meaning that, typically, few mutated genes have been associated with childhood cancers. Moreover, the mutations that have been discovered do not seem to be susceptible to regulation by drugs.


In the current study, the team was the first to identify specific super enhancers (SE) – regions of DNA that drive the over production of certain gene products – in cells from children with AML.

These SE were associated with leukemia-promoting genes and were generally distinct from the previously published SE of adult AML. One SE of specific interest was associated with the gene RARA. Sixty-four percent of the pediatric patient AML samples the researchers studied had this RARA SE.

Yi and her colleagues were excited to find that tamibarotene slowed the proliferation, induced apoptosis or promoted cell maturation in lab cultures of patient AML cells with the RARA SE. In contrast, cells without the RARA SE were not sensitive to the drug.

In addition, tamibarotene extended survival in an animal model of AML with RARA SE, but did not slow cancer growth in an animal model lacking RARA SE.

Our findings support taking the next step toward bringing this potential new treatment to the clinic by conducting a clinical trial of tamibarotene in children with AML having high RARA levels,” said Yi, a member of Baylor’s Dan L Duncan Comprehensive Cancer Center.

Interested in all the details of this study? Find it in the journal Blood Advances.

For a complete list of contributors their affiliations and the financial sources of this work, go to the publication.


By Ana María Rodríguez, Ph.D.


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