Zebrafish models identify high-risk genetic features in leukemia patients

May 10, 2011, University of Utah

Leukemia is the most common childhood cancer; it also occurs in adults. Now researchers working with zebrafish at Huntsman Cancer Institute (HCI) at the University of Utah have identified previously undiscovered high-risk genetic features in T-cell acute lymphocytic leukemia (T-ALL), according to an article published online May 9, 2011, in the cancer research journal Oncogene. When compared to samples from human patients with T-ALL, these genetic characteristics allowed scientists to predict which patients may have more aggressive forms of the disease that either recur after remission or do not respond to treatment.

While there are several subtypes, in all leukemias the body overproduces certain that have not matured properly. In this study, the researchers investigated a particular type of leukemia that results from in , a type of white blood cell found in both humans and zebrafish.

Using a technique called serial transplantation, the research team studied T-ALL in zebrafish and selected from those in which the disease advanced more rapidly for further testing. This method allowed the research team to zero in on genes associated with T-ALL's most aggressive forms. They then compared these genetic features to samples from human patients whose clinical outcomes with T-ALL are known.

"We can cure 80% of the children who come to us with leukemia, but there are 20 percent we cannot cure. Sometime the cures come at a high cost to patients in immediate and delayed side effects from chemotherapy," said Nikolaus Trede, M.D., Ph.D., associate professor in the Department of Pediatrics at the University of Utah (U of U) School of Medicine, HCI investigator, and a senior author of the article. "These results may lead to tests that can show which children with the disease need the strongest chemotherapy to overcome their cancer. Children with less aggressive forms of leukemia can be cured with milder chemotherapy that produces fewer side effects, both during treatment and long after treatment is complete."

Kimble Frazer, M.D., Ph.D., assistant professor of pediatrics at the U of U and a member of the Trede Lab, is co-senior author of the article. "One of the genes identified in the study had not previously been recognized as important in T-ALL," said Frazer. "Another gene, associated with patients whose outcomes were least favorable, has not received enough research attention to even have an official name. It only has an 'address' that tells its location on a specific chromosome."

The researchers stress that their results are still preliminary. They plan further laboratory studies to bolster the case that this unnamed gene with the address C7orf60 is important in the development of T-ALL. Additional zebrafish experiments that focus on this gene could be designed to amplify its effects and confirm its contribution to creating more, or hardier, leukemia. In the end, the research could lead to a test that would allow doctors to determine the best course of treatment for an individual leukemia patient by analyzing a blood sample.

Both Trede and Frazer credit the article's first-listed author, Lynnie Rudner, with much of the work leading to the published results. Rudner is the recipient of the American Medical Association (AMA) Foundation's Seed Grant, one of only 38 individuals nationwide who received a seed grant in 2010, and a student in the U of U's M.D./Ph.D. program, which produces graduates qualified in both clinical practice and laboratory research.

Explore further: Possible new approach to treating deadly leukemia in babies

Related Stories

Possible new approach to treating deadly leukemia in babies

April 13, 2011
A Loyola University Health System study points to a promising new approach to treating an aggressive and usually fatal leukemia in babies.

Recommended for you

Diversity in the brain—how millions of neurons become unique

September 26, 2018
How is it possible that so many different and highly specific neuron types arise in the brain? A mathematical model developed by researchers from the University of Basel's Biozentrum demonstrates that different variants of ...

New Tourette disorder genes come to light

September 25, 2018
In the largest DNA sequencing study of Tourette Disorder (TD) to date, UC San Francisco researchers and their collaborators have unearthed new data suggesting a potential role for disruptions in cell polarity in the development ...

Genetic determinants of telomere length in African American youth

September 25, 2018
Telomeres are DNA-protein structures that play a vital role in maintaining DNA stability and integrity. Telomere length (TL) is an important biomarker of aging and overall health, but TL has been mostly studied in adult populations ...

Genetic testing: Not a one-and-done deal

September 25, 2018
Genetic testing can play a substantial role in medical management by uncovering changes in genes that are associated with an increased risk for hereditary cancers. A new research study from investigators at UT Southwestern ...

Thousands of unknown DNA changes in the developing brain revealed by machine learning

September 24, 2018
Unlike most cells in the rest of our body, the DNA (the genome) in each of our brain cells is not the same: it varies from cell to cell, caused by somatic changes. This could explain many mysteries—from the cause of Alzheimer's ...

Mitochondrial diseases could be treated with gene therapy, study suggests

September 24, 2018
Researchers have developed a genome editing tool for the potential treatment of mitochondrial diseases: serious and often fatal conditions which affect 1 in 5,000 people.

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.