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Pathways to Discovery: Summer 2012

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UCCCC Symposium Explores Breakthroughs in Leukemia

Remarkable progress has been made toward the development of personalized therapies for leukemia, formerly considered one of the most puzzling and devastating cancers. In recent years, powerful genomics research has allowed scientists to define the molecular underpinnings of the disease and develop targeted therapeutics to treat patients more effectively.

The University of Chicago Medicine Comprehensive Cancer Center (UCCCC) hosted a symposium bringing together renowned researchers from the UCCCC and across the nation who shared advances on the latest topics in leukemia research, including epigenetics, genomics, and therapeutics. The symposium, “Molecular and Translational Breakthroughs in Leukemia Research,” was held at the Knapp Center for Biomedical Discovery in April.

“The translational progress that we’ve seen in leukemia started with insights from the group at The University of Chicago 40 years ago,” said Wendy Stock, MD, professor of medicine, who moderated the symposium along with Michael J. Thirman, MD, associate professor of medicine. They are co-leaders of the UCCCC’s Hematopoiesis and Hematological Malignancies Program.

Learning from Pioneers
Clara Bloomfield, MD, one of the most prolific academic physician leaders in the field, delivered the symposium’s keynote address. She is a Distinguished University Professor at The Ohio State University Comprehensive Cancer Center and an alumna of The University of Chicago Pritzker School of Medicine. Dr. Bloomfield was introduced by Janet Rowley, MD, DSc, the Blum-Riese Distinguished Service Professor of Medicine, whose many breakthroughs in understanding the relationship between genetics and cancer opened the door to targeted therapies for leukemias and lymphomas.

Dr. Bloomfield’s keynote address focused on the use of molecular markers to guide the treatment of AML. She said that in the past 5 years, many new prognostic markers were identified and are now routinely being used to “risk stratify” patients. Researchers are beginning to develop therapeutic agents targeted against these biomarkers in appropriate patient subsets. “Novel targetable markers are moving at a rapid pace,” she said, adding that clinical trials provide a leukemia patient’s best chance for survival.

A Broad Perspective of Leukemia
Several UCCCC researchers shared the results of their leukemia research endeavors. Lucy Godley, MD, PhD, associate professor of medicine, described the importance of epigenetic changes in gene regulation and hematopoiesis. Epigenetic modifications, such as the conversion of 5-methylcytosine to 5-hydroxymethylcytosine (5-hmC) in DNA, play an important role in the differentiation of hematopoietic stem cells. Dr. Godley and Chuan He, PhD, professor of chemistry, developed a method to measure the level of 5-hmC in cells precisely. Using this method, further studies will reveal how changes in 5-hmC levels alter gene expression and contribute to the development of leukemia.

Kenan Onel, MD, PhD, associate professor of pediatrics, described a new way to think about cancer risk that may have ramifications for individualizing cancer therapy. He recently performed a genome-wide association study of patients who developed radiation therapy induced second cancers, such as breast cancer or thyroid cancer following treatment for Hodgkin lymphoma. He found that individuals with the risk version of a variant in a gene called PRDM1 had as much as a 30% chance of developing these second cancers, whereas those who had the protective version of the variant had only a 3% chance. This effect of the variant on cancer risk was only observed, however, in patients who were treated with radiation. This means that genetic variation associated with increased cancer risk needs to be thought of in the context of treatment exposures rather than in isolation.

Screening for these variants could help clinicians develop personalized interventions to prevent second cancers, by altering the treatment of first cancers, and may also have implications toward the risk of first cancers.

Another UCCCC participant, Olatoyosi Odenike, MBBS, associate professor of medicine, commented on the promise of epigenetic therapies for patients with AML and other myeloid neoplasms. Dr. Odenike led a number of clinical trials involving drugs that target epigenetic changes in cancer cells, including a Phase I multicenter trial that evaluated the combination of two epigenetic agents, belinostat and azacitidine. The combination was well tolerated and showed promising clinical activity. She said that future directions for her research include identifying additional targets for clinical development and finding predictive biomarkers and signatures.

Other speakers included Ari Melnick, MD, associate professor of medicine at Weill Cornell Medical College, Jean-Pierre Issa, MD, director of the Fels Institute for Cancer Research and Molecular Biology at Temple University, Victoria Richon, PhD, vice president of biological sciences at Epizyme Inc., and James Bradner, MD, assistant professor of medicine at Harvard Medical School.

“We were truly privileged to have outstanding speakers who presented groundbreaking research in leukemia biology and therapy,” said Dr. Thirman. “I think that many in the audience came away with new ideas to test in their own laboratories based on the data presented.”

Ernst Lengyel