Research Highlights - Promise Winter 2014

Dr. Evans announces retirement plans

St. Jude patients pull out notepads and don their journalist hats to interview Dr. William E. Evans, St. Jude director and CEO, as he announces his plan to retire as the hospital’s CEO in July 2014. Evans, who began his career at St. Jude in 1972 and became CEO in 2004, will continue to lead his research laboratory at St. Jude after retiring from the CEO position.

Can childhood cancer survivors lower heart risks?

Treatments that are excellent at fighting cancer can sometimes be hard on the heart. As a result, childhood cancer survivors are much more likely than others to experience serious cardiac problems as adults.

The good news is that survivors may be able to lower their risk of heart problems by taking specific action. New research led by St. Jude shows that cancer survivors may benefit from staying in a healthy range for blood pressure, weight, blood sugars and blood lipids like cholesterol.

The findings are based on data from more than 10,000 childhood cancer survivors and were published in the Journal of Clinical Oncology. “For doctors who are caring for survivors, the key message from this study is that aggressive management of hypertension is especially important for this population,” said Greg Armstrong, MD, of St. Jude Epidemiology and Cancer Control.

Downing elected to Institute of Medicine

James Downing, MD, scientific director, deputy director and executive vice president, has been elected to the Institute of Medicine (IOM), a prestigious branch of the National Academy of Sciences.

“Dr. Downing’s election to the Institute of Medicine is a great testament to his many scientific accomplishments and a great honor for St. Jude,” said Dr. William E. Evans, St. Jude director and CEO.

Downing is internationally recognized for his seminal contributions to understanding the molecular pathology of acute leukemia and the application of this information to increase the number of children cured. In 2010, he was instrumental in launching the St. Jude Children’s Research Hospital – Washington University Pediatric Cancer Genome Project, the world’s largest project devoted to understanding the genetic origins of childhood cancers.

St. Jude has one of the highest numbers of IOM members among U.S. children’s hospitals. Other IOM members from St. Jude are Nobel Laureate Peter Doherty, PhD; Director and CEO Dr. William E. Evans; Arthur Nienhuis, MD, former St. Jude CEO; Charles Sherr, MD, PhD, Howard Hughes Medical Institute Investigator and Tumor Cell Biology chair; and Mary Relling, PharmD, Pharmaceutical Sciences chair.

Fight cancer, not yourself

The body’s immune system does much more than fight off colds. It can also fight cancer. Immunotherapies seek to harness and enhance this power of the immune system to kill cancer cells. But care must be taken in developing the therapies, because misguided immune activity can attack healthy tissue.

St. Jude scientists have discovered a way to direct the immune system to shrink or eliminate tumors without causing autoimmune problems later. The work, published in the journal Nature, focused on white blood cells called regulatory T cells. These cells guard against autoimmune and inflammatory disease, but can also interfere with the immune system’s cancer-fighting ability.

Dario Vignali, PhD, St. Jude Immunology vice chair, and his colleagues found a way to uncouple these two functions of regulatory T cells. “We may now have an opportunity to selectively target the activity of regulatory T cells for treatment of cancer without inducing autoimmune or inflammatory complications,” he said.

Endless immune cells, created in a petri dish

Your immune system is exquisitely complex, made of many different types of cells with specific jobs. A major scientific challenge has been to figure out how each type of immune cell develops and carries out its job.

This challenge may have just gotten easier, thanks to a breakthrough from St. Jude scientists, reported in the journal Nature Methods. By adding two factors to bone marrow preparations, researchers found they could generate an unlimited supply of immune cells in the laboratory. This simple method, which can be used to create a variety of key immune cell types, opens a new avenue to pursue research on the immune system and immune-based therapies.

“This is a terrific system to answer many basic questions related to immune cell development and differentiation, or immune cell function,” said Hans Haecker, MD, PhD, of St. Jude Infectious Diseases. “Although this is a preclinical system, we are already dreaming of the therapeutic applications.”

Putting the “ME” in social media

Morinsola Keshinro of St. Jude Child Life (right) works with Paishence Watkins during “All of Me Week” activities. This year’s theme was social media, with each activity incorporating the world of technology. The week’s events concluded in a show-and-tell reception that featured patients’ finished products on display along with a video compilation.

Survivors may face early aging

Feeling exhausted? Having trouble getting off the couch? Many people might voice these complaints after a tough day at work. But for childhood cancer survivors, these symptoms may be signs of something more serious: premature aging.

A surprising number of young adult survivors showed signs of early aging, or frailty, in a recent study conducted at St. Jude. The study tested 1,922 survivors for strength, muscle mass, fatigue and other measures. In a comparison group of 341 adults who did not have cancer as children, no frailty was reported.

Survivors should use these findings as motivation to take action, emphasized Kirsten Ness, PhD, of St. Jude Epidemiology and Cancer Control. “This is an opportunity for them to take control and start working with their health care providers on ways to improve their fitness,” she said.

The research, published in the Journal of Clinical Oncology, underscores the importance of work now underway at St. Jude on the best methods to combat frailty in childhood cancer survivors.

Sickle cell drug cuts health costs for patients

A drug that is effective in treating sickle cell anemia led to reduced hospitalizations for affected infants and toddlers and cut their annual estimated medical costs by 21 percent, according to an analysis led by St. Jude. The report appeared in the journal Pediatrics.

The study is the largest ever to focus on the economic impact of the drug hydroxyurea in children with the inherited blood disorder. The result supports expanded use of the drug to extend the length and quality of life for sickle cell anemia patients of all ages, said Winfred Wang, MD, of St. Jude Hematology. Wang led the multicenter clinical trial known as BABY HUG.

“We estimate that hydroxyurea cut overall annual medical expenses by about $3,000 for each patient by helping them avoid disease complications that require inpatient hospital care,” Wang said. “We expect those savings will grow along with patients, whose symptoms often increase in severity and frequency as they age.”

Counted blessings

St. Jude chaplains (from left) Kimberly Russell, Mark Brown, Brent Powell and Walter Spears bless the hands of employees and families during the annual Blessing of the Hands. The event is held each year in recognition of Spiritual Care Week.

Taking aim at Lou Gehrig disease

Amyotrophic lateral sclerosis (ALS), also known as Lou Gehrig disease, is diagnosed in about 5,600 Americans each year. With no effective treatment, ALS causes progressive deterioration of nerve cells in the brain and spine and usually leads to death within five years of diagnosis.

St. Jude scientists and their collaborators have discovered an important clue to ALS that may provide new hope for developing treatments. Previous work from the St. Jude team found that mutations in a gene called VCP lead to ALS, but it was not clear why. The new work revealed that VCP mutations cause a toxic buildup of proteins and other materials inside nerve cells, potentially pointing to how these mutations trigger disease.

“The results go a long way toward explaining the process that links a variety of neurodegenerative diseases, including ALS, frontotemporal dementia and related diseases,” said J. Paul Taylor, MD, PhD, of St. Jude Developmental Neurobiology.

The findings were published in the journal Cell.

Native American ancestry influences leukemia risk

How does ethnic background affect a child’s risk of developing and surviving cancer?

Jun Yang, PhD, of St. Jude Pharmaceutical Sciences and his colleagues have linked an inherited gene variation to a nearly four-fold increased risk of developing a deadly subtype of pediatric acute lymphoblastic leukemia (ALL).

The subtype, Philadelphia chromosome-like ALL, accounts for as much as 15 percent of childhood ALL and is associated with a high risk of relapse and a poor outcome. The high-risk variant was found in the GATA3 gene.

Hispanic Americans and others whose genetic profile suggested Native American ancestry were more likely to have the high-risk variant than those from other ethnic backgrounds. The study’s findings highlight how inherited and tumor genetic variants may work together to influence a person’s risk of developing and surviving cancer.

The findings were published in Nature Genetics.

A new look at an old drug: Improving AML survival

The quest to push cure rates for children with acute myeloid leukemia (AML) recently got a boost from a study led by St. Jude. The study, published in the journal Cancer, took a new look at an old drug.

The drug, trade named Mylotarg, was withdrawn from the market in 2010 due to concerns about its safety and effectiveness. But scientists found that the drug likely helped children with highrisk AML who received the medication while it was on the market.

Mylotarg targets AML cells that carry a certain protein on their surface. St. Jude investigators are working to develop new treatments that target the same protein. The research may provide desperately needed new agents to help AML patients whose cancer returns or persists. “The results of this and earlier studies make a strong case that some patients benefit from this targeted therapy,” said Jeffrey Rubnitz, MD, PhD, of St. Jude Oncology.

Abridged from Promise, Winter 2014

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