Research Highlights - Promise Spring 2013


Promise Autumn 2012 Highlight

DNA variations linked to relapse risk 
One of the largest studies of the role inherited genetic variation plays in the treatment outcome of young acute lymphoblastic leukemia (ALL) patients has linked more than 100 common differences to an increased risk of relapse.

Masters of the mask 
Jason Garrett Jr. and Payton Buford Peter create Mardi Gras-themed masks and decorations in the Patient Care Center lobby to celebrate Fat Tuesday.

Scientists unfold mysteries of cell-suicide pathway
Like a cat that loosens its grip just long enough for a mouse to escape, a protein named PUMA frees the pivotal tumor suppressor protein p53, researchers have discovered.

Visiting Memphis? Give blood or platelets 
Located within the hospital, St. Jude Blood Donor Center helps ensure that St. Jude patients always have access to blood products.

Researchers study effects of drug shortage 
St. Jude has blown the whistle on the impact that drug shortages can have on children receiving cancer treatment.

Discovery points way to revised screenings 
St. Jude researchers have found evidence that chest irradiation may leave some adult survivors of childhood cancer in danger of developing pulmonary hypertension during middle age.

On-stage serenade 
AB Quintanilla, lead singer of Kumbia All Stars, serenades St. Jude patient Yazleemar Gonzalez Santana during the 11th annual Promesa y Esperanza Seminar.

Scientists aim to protect vulnerable patients from flu 
Doubling the doses of pandemic influenza vaccine and booster shots gave children and young people infected with the human immunodeficiency virus (HIV) enhanced protection against the 2009 H1N1 pandemic flu virus.

St. Jude receives national honors 
St. Jude recently received kudos from two national magazines.


DNA variations linked to relapse risk

One of the largest studies of the role inherited genetic variation plays in the treatment outcome of young acute lymphoblastic leukemia (ALL) patients has linked more than 100 common differences to an increased risk of relapse.

Investigators hope the discovery will lead to better detection of young ALL patients facing the highest odds of relapse and new strategies for preventing it.

A substantial number of children with ALL relapse even though they are considered at low risk based on current factors. Of those who relapse, fewer than half are still alive after five years. More accurate risk classification would help clinicians individualize therapy and improve survival for these patients.

The study, led by St. Jude investigators, identified 134 small, common variations in genes as predictors of relapse. Among those findings, scientists discovered that a single change in the PYGL gene was associated with nearly a four-fold increased risk of relapse.

Jun J. Yang, PhD, Pharmaceutical Sciences, was first author of a report on this project, which appeared in the journal Blood. Mary Relling, PharmD, Pharmaceutical Sciences chair, was senior author.

“Most cancer specialists have concentrated their work on the genetic variations of the cancer cells themselves that identify higher-risk forms of leukemia,” Relling said. “Our study shows that genetic variations that are inherited from the parents—variations that make us differ from each other—also play a big role in why leukemia relapses occur in some patients but not others.”

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 Jason Garrett Jr. and Payton Buford Peter

Masters of the mask

Jason Garrett Jr. and Payton Buford Peter create Mardi Gras-themed masks and decorations in the Patient Care Center lobby to celebrate Fat Tuesday. In the Mardi Gras event organized by the St. Jude Child Life program, children donned masks and paraded through the hospital’s hallways, as cheering employees distributed beads and high-fives.

Scientists unfold mysteries of cell-suicide pathway

Like a cat that loosens its grip just long enough for a mouse to escape, a protein named PUMA frees the pivotal tumor suppressor protein p53, researchers have discovered. The escape activates a pathway that leads cells to self-destruct.

That finding may help scientists in their ongoing efforts to harness the body’s cell-suicide (apoptotic) machinery to get rid of tumor cells.

St. Jude researchers reported that PUMA acts through a mechanism called regulated unfolding to set p53 loose to switch on the apoptotic pathway. The body uses apoptosis to eliminate damaged, unneeded or unwanted cells, including emerging tumor cells. Investigators found PUMA induces partial unfolding of BCL-xL, a protein that normally binds p53 and keeps this critical tumor suppressor under wraps.

The findings were published in a recent issue of Nature Chemical Biology.

The results build on previous St. Jude research on how apoptosis is regulated. The work also suggests that regulated unfolding is a general mechanism that likely controls signaling along other pathways in cells. Richard Kriwacki, PhD, of St. Jude Structural Biology, and Douglas Green, PhD, Immunology chair, are the study’s co-corresponding authors.

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Visiting Memphis? Give blood or platelets

Dan Medley relaxes during a recent donation at the St. Jude Blood Donor Center. Located within the hospital, the facility helps ensure that St. Jude patients always have access to blood products.

“About 1,000 blood product Dan Medley and Kimberly Fostertransfusions are performed during a typical month at St. Jude,” said Kimberly Foster (pictured at right) of the Blood Donor Center. “Each unit of donated whole blood saves the hospital about $250, which is what one unit costs if it must be purchased from an outside source. Each platelet donation saves St. Jude between $500 and $700.”

For more information, visit www.stjude.org/blood-donor-center or call 1-866-278-5833, ext. 2024.

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Researchers study effects of drug shortage

St. Jude has blown the whistle on the impact that drug shortages can have on children receiving cancer treatment.

Monika Metzger, MD, of St. Jude Oncology, led a multi-institutional team that studied what happens to children who must receive substitute cancer-fighting drugs because of national drug shortages.

The researchers found that two-year cancer-free survival for children, teens and young adults enrolled in a Hodgkin lymphoma clinical trial fell from 88 to 75 percent after the drug cyclophosphamide was substituted for mechlorethamine. The patients were receiving treatment for intermediate- or high-risk disease. The substitution occurred after a mechlorethamine shortage that began in 2009.

No patients in the study died, but those who relapsed received additional intensive therapy that is associated with higher odds for infertility and other health problems later.

An analysis comparing how patients in each group were faring two years after their cancer diagnoses appeared in the New England Journal of Medicine. The report provides the first evidence of a drug shortage adversely impacting treatment outcomes in specific patients. St. Jude led the study for the five institutions in the Pediatric Hodgkin Lymphoma Consortium.

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Discovery points way to revised screenings

St. Jude researchers have found evidence that chest irradiation may leave some adult survivors of childhood cancer in danger of developing pulmonary hypertension during middle age.

Childhood cancer survivors treated with chest irradiation or certain chemotherapy drugs are known to be at risk for a variety of treatment-related heart problems. But the study, published recently in the Journal of Clinical Oncology, is the first report suggesting survivors might also face higher odds of developing pulmonary hypertension. Pulmonary hypertension is a serious, progressive form of increased pressure in the arteries in the lungs.

First author Gregory Armstrong, MD, of St. Jude Epidemiology and Cancer Control, said pulmonary artery pressure was elevated in 25 percent of adult survivors in the study who had received chest irradiation.

The findings suggested the survivors might be at higher risk of pulmonary hypertension. Researchers also found that the risk climbed with increasing radiation dose and was associated with decreased exercise endurance. This finding represents important information for clinicians monitoring cardiovascular health of adult survivors of childhood cancer.

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  AB Quintanilla with St. Jude patient Yazleemar Gonzalez Santana

On-stage serenade

AB Quintanilla, lead singer of Kumbia All Stars, serenades St. Jude patient Yazleemar Gonzalez Santana during the 11th annual Promesa y Esperanza Seminar. Latin music artists, representatives from 15 Spanish-language TV stations and many celebrity guests joined St. Jude radio partners for the event. Since its inception in 1997, Promesa y Esperanza has raised more than $88 million for the hospital.

Scientists aim to protect vulnerable patients from flu

Doubling the doses of pandemic influenza vaccine and booster shots gave children and young people infected with the human immunodeficiency virus (HIV) enhanced protection against the 2009 H1N1 pandemic flu virus, according to a national study led by St. Jude investigators. The approach sparked antibody production sufficient to protect more than 80 percent of participants against the pandemic flu strain.

The findings suggest the same strategy might help protect vulnerable patients in future flu pandemics. Individuals with immune systems weakened by cancer treatment, HIV infection or other causes are at greater risk of contracting the flu and are more likely to require hospitalization.

Patricia Flynn, MD, Infectious Diseases, is the first and corresponding author of the research, which was published in the Journal of Infectious Diseases.

The study is one of two published recently that reflects ongoing efforts at St. Jude to develop new, more effective strategies to protect patients against flu infections. Hana Hakim, MD, Infectious Diseases, is first and corresponding author of the second study, which appeared in the journal Vaccine.

Work continues on making flu vaccinations more effective for high-risk patients. Hakim said it remains important for those who care for or live with these children to be vaccinated.

“Because of their weak immune systems, if these children are exposed to the flu they are more likely to catch it. If they become infected, they are more likely to be hospitalized for complications than healthy children are,” Hakim said.

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St. Jude receives national honors

St. Jude recently received kudos from two national magazines. The hospital was recognized for the third consecutive year by FORTUNE magazine as one of the “100 Best Companies to Work For.” Hospital employees consistently cite the pride they have in the St. Jude mission as a top benefit.

“Our 50 years of progress has come from teamwork, and our employees know that regardless of which department they work in, they are valued and they understand their efforts contribute directly to achieving our mission,” said Dr. William E. Evans, St. Jude director and CEO.

St. Jude was also named one of the best cancer care hospitals in the country by Parents magazine. Based on published research data, St. Jude has the best worldwide outcomes in a number of pediatric cancer categories, including acute lymphoblastic leukemia, acute myeloid leukemia and medulloblastoma.

“Being recognized is always a great honor, especially since our focus on some of the toughest pediatric cancers often makes comparisons difficult,” Evans said. “This recognition is a tribute to the tireless dedication of all of our physicians, researchers and staff who help families facing the most challenging times imaginable.”

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Abridged from Promise, Spring 2013


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