Highlights - Promise Autumn 2012


Promise Autumn 2012 Highlight

 


Closing AML’s age-related survival gap

Modern, risk-adapted therapies are shrinking the survival gap between younger patients with acute myeloid leukemia (AML) and adolescents and teenagers battling the same disease, according to a St. Jude analysis.

Patients treated as part of the most recently completed St. Jude AML protocol enjoyed similar, high survival rates regardless of their age. Older patients were also just as likely as children ages 9 and younger to be cancer free three years after diagnosis. The results are an improvement from the 1990s, when AML patients ages 10 through 21 fared worse than younger patients at St. Jude and nationwide.

The past decade has brought a marked improvement in survival for pediatric AML patients, including older patients.

“In this study we show for the first time that there is no longer a significant difference in outcome between younger and older patients with this disease and that the relapse rates are nearly identical,” said Jeffrey Rubnitz, MD, PhD, of St. Jude Oncology. Rubnitz is the first and corresponding author of a report on the study, which appeared in the journal Cancer.

The challenge now is to reduce treatment-related deaths, which are nearly three times more likely to strike adolescent AML patients than their younger counterparts.

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Discovery may yield new flu drugs

St. Jude scientists have reported details of how certain drugs can target and inhibit an enzyme essential for replication of the influenza virus. All strains of influenza require the enzyme. Researchers believe their findings will yield drugs that can effectively treat new strains of the virus, which may be resistant to current antiviral treatments. The findings may also help scientists develop drugs that impede the virus’ ability to develop drug resistance in the first place.

Stephen White, DPhil, chair of the hospital’s Structural Biology department, and Thomas Webb, PhD, of St. Jude Chemical Biology and Therapeutics, were senior authors of a report on this study, which appeared in the journal PLoS Pathogens.

Researchers will use information gleaned from this study to design improved compounds that could be drug candidates for pre-clinical and clinical testing. The St. Jude team will work with a pharmaceutical company to further develop and test drugs. Once in clinical use, the drugs would offer a valuable and widely used first strike against the influenza virus.

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Ready, aim, get silly

Silly String

St. Jude patients take aim during a Silly String war held as part of the annual Silly Field Day hosted by the hospital’s Child Life program. Research has shown that play promotes children’s growth and development, and helps patients to continue achieving developmental milestones while receiving treatment. Each summer, Silly Field Day provides an eagerly anticipated stress-buster for kids and families, as well as staff.

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Exploring the life and death of cells

St. Jude-led research provides new evidence of how a protein complex functions like a puppet master during embryonic development, determining not only if cells live or die but possibly the nature of that cell death as well.

The complex includes the proteins FADD, caspase-8 and FLIP. Investigators showed that these and other proteins in the complex work together to prevent programmed cell death. The same complex can also block activity of an enzyme that is linked to another cell death pathway. The findings offer clues into how cells foil the spread of viral infections and possible strategies for prompting malignant cells to self-destruct.

The results also provide insight into normal development and further the understanding of both the protein complex and a form of cell death called necrosis. Until recently, necrosis was considered to be an un-programmed form of cell death resulting from an accident or injury. Now, however, it is viewed as a distinct form of cell suicide the body uses to rid itself of damaged, dangerous or unneeded cells.

A report on this topic appeared in the journal Cell Reports. Douglas Green, PhD, St. Jude Immunology chair, and postdoctoral fellow Christopher Dillon, PhD, were corresponding author and first author, respectively.

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Survivors’ fracture risk lower than anticipated

As childhood cancer survivors head into middle age, they are no more likely than their siblings to report having broken bones. That finding is good news for the growing ranks of pediatric cancer survivors.

Earlier studies suggested that adult survivors of childhood cancer might be at particularly high risk of fractures due to diminished bone mineral density and other bone changes caused by irradiation or certain chemotherapy agents. But the largest study yet of adult survivors of childhood cancer suggests that is not the case. After adjusting for factors such as age, ethnicity, smoking and use of medications to promote bone health, childhood cancer survivors were less likely than their siblings to report having broken at least one bone in their lifetime.

Carmen Wilson, PhD, a postdoctoral fellow in St. Jude Epidemiology and Cancer Control, was the first and corresponding author of an article on this project, which was featured in the journal Cancer. The research was part of the Childhood Cancer Survivor Study, a federally funded collaboration headquartered at St. Jude that includes 30 U.S. and Canadian institutions.

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Tony Thomas, Terre Thomas, Marlo Thomas with St. Jude patient Miguel Betances Lee

Celebrating in style

St. Jude continued its yearlong 50th anniversary celebration with an official ribbon-cutting ceremony for the Danny Thomas/ALSAC Pavilion, which recently underwent a renovation. From left, Tony, Terre and Marlo Thomas tour the facility with St. Jude patient Miguel Betances Lee.

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Taking aim at bacterial infections

Research led by St. Jude scientists has identified a possible new approach to defeating bacterial infections by targeting an innate immune system component in a bid to invigorate the immune response.

Despite the availability of antibiotics, bacterial infections continue to extract a heavy toll of suffering and death. A better understanding of how the immune system recognizes and responds to infectious agents will aid efforts to develop new, more effective treatments. In the St. Jude study, researchers demonstrated the primary function of an innate immune molecule named NLRP6 and showed how the protein works to impede bacterial clearance.

“This discovery offers a completely new approach to fighting infections by targeting the host immune response rather than the bacterium,” said Thirumala-Devi Kanneganti, PhD, of St. Jude Immunology. She was senior and corresponding author of a report on this study, which appeared in the scientific journal Nature.

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Healthy weight is best

St. Jude research indicates that overweight and obese children are less likely than those of normal weight to survive acute myeloid leukemia (AML) and more likely to die from treatment-related infections.

The study also found underweight patients had higher rates of treatment-related mortality and lower rates of survival than patients with healthy body mass indexes (BMIs).

“Although survival rates for pediatric AML have improved in the last 25 years, they remain below 80 percent. These results suggest BMI may help us identify patients who are at higher risk for infections and who might benefit from additional supportive care,” said Hiroto Inaba, MD, PhD, of St. Jude Oncology. He is the first and corresponding author of the study, which was published in the journal Cancer.

Researchers found a significant connection between BMI and overall survival, even when other disease risk factors were taken into consideration.

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Radiation dose tied to colorectal cancer risk

St. Jude researchers recently discovered that the colorectal cancer risk facing aging childhood cancer survivors is linked to the dose of abdominal radiation they received as children and the amount of colon that was irradiated.

Although previous studies linked childhood radiation therapy to an increased risk of second cancers, this analysis showed the risk of colorectal cancer was associated with the radiation dose. Scientists reported for the first time that the greater the volume of colon tissue exposed to radiation, the greater the risk of colorectal cancer. Treatment with drugs known as alkylating agents was associated with a nearly nine-fold increased risk of secondary colorectal cancer.

The results underscore the importance of cancer screenings and possibly the need to revisit current screening guidelines. “Colonoscopy offers a proven method of detecting colorectal cancer early, offering survivors and others their best chance of cures,” said Kerri Nottage, MD, of St. Jude Hematology, co-first author of a report in Journal of Clinical Oncology. “Yes, childhood cancer survivors are at higher risk of developing this cancer, but they can take steps to protect themselves.”

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David McKeeDavid McKee leaves mighty legacy

St. Jude and ALSAC mourn the death of David L. McKee, who served ALSAC for 35 years in positions that included interim CEO and chief operating officer.

McKee, who died August 17, was instrumental in the creation of a number of fundraising programs and initiatives, including Country Cares for St. Jude Kids, one of ALSAC’s most successful fundraising programs. Recipient of the 2011 Lifetime Achievement Award by Fundraising Success magazine, he helped lead ALSAC to record growth and its current status as the second largest health care charity in America.

Gifts to St. Jude in memory of McKee may be made by visiting fundraising.stjude.org/goto/davemckee or by calling (800) 873-6983.

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Reprinted from Promise Autumn 2012

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