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Huntsman Cancer Institute at the University of Utah
PRESS RELEASE
For Immediate Release
May 10, 2011
Contact:
Linda Aagard
Huntsman Cancer Institute
(801) 587-7639
Zebrafish Models Identify High-Risk Genetic Features in Patients with Leukemia
Identified genes predict worst case scenarios
SALT LAKE CITY—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 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 blood cells that
have not matured properly. In this study, the researchers investigated a particular type of
leukemia that results from genetic mutations in T-cells, 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 cancer cells 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% 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. Other co-authors
include researchers from Brigham and Women’s Hospital in Boston, Massachusetts, University
of Texas at Brownsville, Dana-Farber Cancer Institute and Children’s Hospital Boston, and St.
Jude Children’s Research Hospital in Memphis, Tennessee.
This work was supported by funding from the National Institute of Allergy and Infectious
Diseases, the Eunice Kennedy Shriver National Institute of Child Health & Human
Development, the American Medical Association, Huntsman Cancer Foundation, the Children’s
Health Research Center at the University of Utah, and Huntsman Cancer Institute core facilities.
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The mission of Huntsman Cancer Institute (HCI) at The University of Utah is to understand
cancer from its beginnings, to use that knowledge in the creation and improvement of cancer
treatments, to relieve the suffering of cancer patients, and to provide education about cancer risk,
prevention, and care. HCI is a National Cancer Institute-designated cancer center, which means
that it meets the highest national standards for cancer care and research and receives support for
its scientific endeavors. HCI is also a member of the National Comprehensive Cancer Network
(NCCN) a not-for-profit alliance of the world’s leading cancer centers, which is dedicated to
improving the quality and effectiveness of care provided to patients with cancer. For more
information about HCI, please visit www.huntsmancancer.org.