Research Highlights - Promise Winter 2013


Research Highlights
 

New treatment options for Ph-like AML
St. Jude scientists have identified new genetic alterations underlying a high-risk subtype of leukemia that could be effectively targeted with existing therapies.

Colorful creations
During All of Me Week at St. Jude, patients and their siblings engaged in a variety of activities to express themselves.

Exciting AMKL discovery
Researchers have identified an abnormal gene responsible for almost 30 percent of a rare subtype of acute myeloid leukemia (AML) that has a grim prognosis.

Focusing on Glomulin
A faulty gene linked to a rare blood vessel disorder has led St. Jude scientists to discover a mechanism involved in determining the fate of possibly thousands of proteins working inside cells.

The risk of swine viruses
St. Jude-led research has found evidence that the main strains of the influenza virus circulating in North American pigs have the potential to not only infect and sicken humans, but to spread easily from person to person.

Survivors Day Conference
The 2012 Survivors Day Conference dynamic panel discussions with distinguished medical experts, cancer researchers and advocates, as well as other survivors of childhood cancers.

A better way of testing
Research led by St. Jude investigators has identified the best test for measuring early treatment response and guiding therapy.


New treatment options for Ph-like ALL

St. Jude scientists have identified new genetic alterations underlying a high-risk subtype of leukemia that could be effectively targeted with existing therapies.

The study focused on a subtype of acute lymphoblastic leukemia (ALL) known as Philadelphia chromosome-like ALL (Ph-like ALL). This subgroup accounts for as much as 15 percent of childhood ALL. While approximately 90 percent of newly diagnosed ALL patients are cured with current treatments, only 63 percent of patients with Ph-like ALL are alive and cancer-free after five years.

The research identified new alterations in genes that regulate how cells grow and proliferate.

Investigators also showed that the leukemia cells were sensitive to the drugs imatinib and dasatinib, which are already being used against other leukemias, but not this subtype. The findings suggest patients with Ph-like ALL may benefit from the addition of these drugs to current chemotherapy regimens.

“One of the next steps will be to continue work on laboratory tests to rapidly identify patients whose cancer cells carry these alterations and to develop clinical trials to test targeted therapies,” said Charles Mullighan, MBBS (Hons), MSc, MD, Pathology, a corresponding author of the study, which appeared in the journal Cancer Cell.

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Colorful creations

During All of Me Week at St. Jude, patients and their siblings engaged in a variety of activities to express themselves. Anthony Lopez loads up a roller with fresh paint during a project in which participants decorated a giant canvas with their handprints and footprints. The final result was on display during a special reception that featured the canvas as well as videos, poems and songs created during the week.

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Exciting AMKL discovery

Research led by the St. Jude Children’s Research Hospital–Washington University Pediatric Cancer Genome Project has identified an abnormal gene responsible for almost 30 percent of a rare subtype of acute myeloid leukemia (AML) that has a grim prognosis. The subtype, acute megakaryoblastic leukemia or AMKL, accounts for about 10 percent of AML.

The finding offers the first evidence of a genetic mistake that gives rise to a significant percentage of AMKL cases in children. The discovery paves the way for desperately needed treatment advances.

The study identified an abnormal protein that sets certain blood cells on the path to AMKL. The protein is the product of a fusion gene created when pieces of CBFA2T3 and GLIS2 are brought together by the rearrangement of chromosome 16. The fusion gene, found only in children with AMKL, identifies those at high risk for a poor outcome.

“The discovery of the CBFA2T3-GLIS2 fusion gene in a subset of patients with AMKL paves the way for improved diagnostic testing, better risk stratification to help guide treatment and more effective therapeutic interventions for this aggressive childhood cancer,” said James Downing, MD, St. Jude scientific director. Downing was corresponding author of a report on this study, which appeared in the journal Cancer Cell.

To learn more about the genome project, visit www.pediatriccancergenomeproject.org.

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Focusing on Glomulin

A faulty gene linked to a rare blood vessel disorder has led St. Jude scientists to discover a mechanism involved in determining the fate of possibly thousands of proteins working inside cells. The findings highlight a potential new approach for developing treatments for glomuvenous malformations, which result in veins that cause discolored raised skin lumps that can be painful and disfiguring.

The study provides insight into one of the body’s most important regulatory systems, the ubiquitin system. Cells use it to get rid of unneeded proteins. Problems in this system have been tied to cancers, infections and other diseases.

Researchers demonstrated how a protein named Glomulin binds to a key component of the regulatory system. Scientists showed not only where Glomulin binds but also how binding shuts down a biochemical cascade that tags unnecessary proteins for dismantling.

“We believe Glomulin may represent the tip of the iceberg. There could be many proteins that work in this fashion,” said Brenda Schulman, PhD, of St. Jude Structural Biology and a Howard Hughes Medical Institute investigator. She was senior and corresponding author of a report on this work that appeared in the journal Molecular Cell.

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The risk of swine viruses

St. Jude-led research has found evidence that the main strains of the influenza virus circulating in North American pigs have the potential to not only infect and sicken humans, but to spread easily from person to person.

The study focused on triple-reassortant influenza A swine flu viruses, which contain genes from human and bird as well as swine flu viruses. These viruses have caused sporadic illness in individuals who came in contact with infected pigs, but the viruses have not spread from person to person.

In the journal PLoS Pathogens, researchers published evidence that this pattern could change. If confirmed, the findings suggest the strains pose a risk to humans. The work also highlights a potential new method of identifying risky swine flu viruses.

“This study underscores the need to track flu viruses in swine and step up efforts to contain viruses that pose a risk to humans,” said the paper’s corresponding author, Richard Webby, PhD, Infectious Diseases.

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Survivors Day Conference

During the 2012 Survivors Day Conference, cancer survivor Jarrud Falor displayed a photo of himself with St. Jude founder Danny Thomas. Honoring the hospital’s 50th anniversary, the conference featured dynamic panel discussions with distinguished medical experts, cancer researchers and advocates, as well as other survivors of childhood cancers. 

View the event’s webcast at www.stjude.org/survivors2012.

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A better way of testing

Early treatment response is a powerful predictor of long-term outcome for young patients with acute myeloid leukemia (AML). That information can help physicians decide if a more intensive approach is needed. Research led by St. Jude investigators has identified the best test for measuring that response and guiding therapy.

The method uses a laboratory technique called flow cytometry, which makes it possible to identify a single cancer cell in 1,000 normal cells in patient bone marrow. St. Jude investigators were instrumental in developing the test to identify extremely low levels of cancer called minimal residual disease.

Researchers showed that checking for minimal residual disease by flow cytometry is better than two other widely used methods for predicting AML patient survival. The results help identify who might benefit from more intensive therapy, including bone marrow transplantation.

“These results will help establish flow cytometry testing for minimal residual disease as a routine tool for guiding therapy of acute myeloid leukemia and identifying patients early who are at risk of treatment failure,” said Hiroto Inaba, MD, PhD, of St. Jude Oncology. He was the first and corresponding author of an article on the topic that appeared in the Journal of Clinical Oncology.

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