Tim Ley

Advancing Human Health

When Lukas Wartman, MD, came to Washington University as a medical student, he knew he wanted to treat patients with cancer and study the genetic changes underlying the disease. What he didn't know was that by his fourth year of medical school, he would be battling the same disease in which he planned to specialize: leukemia. In 2003, at age 25, Wartman was diagnosed with acute lymphoblastic leukemia, a blood cancer that is treatable in children but often fatal in adults.

After two years of chemotherapy at the university’s Siteman Cancer Center, Wartman’s leukemia was in remission. He finished his clinical training, but in 2008 the leukemia returned. This time, Wartman received intensive chemotherapy and a stem cell transplant from his younger brother, which put the leukemia into remission. Soon after, he began a fellowship in the laboratory of Washington University oncologist Timothy Ley, MD, Lewis T. and Rosalind B. Apple Professor of Medicine and Section Chief of Stem Cell Biology in the Division of Oncology.

For another three years, Wartman remained cancer free, but in 2011 just as he joined the medical school’s oncology faculty, his leukemia returned. This time, no good treatment options existed to beat a second recurrence of his cancer, and there was little hope he would survive. Wartman’s doctors tried a round of experimental chemotherapy and an infusion of his brother’s stem cells, but they did not induce another remission. Time was running out.

That’s when Ley suggested that Wartman join a School of Medicine research study to investigate the genetic makeup of his type of leukemia. Several years earlier, Ley, along with Richard Wilson, PhD, and Elaine Mardis, PhD, at the university’s Genome Institute, had pioneered the sequencing of cancer patients’ genomes as a way to unravel the genetic roots of the disease.

Since then, they have sequenced the complete DNA – called the genome – of tumor cells from more than 1,000 cancer patients enrolled in clinical studies. This endeavor is giving scientists an unprecedented look at the mutations at the root of each patient’s disease. Increasingly, their research suggests that cancers should be classified and treated based on the genes that drive a tumor’s growth, rather than its location in the body.

As part of the research study, the scientists sequenced the genome of Wartman’s tumor cells, and as a comparison, the genome of his healthy cells. At the same time, they also analyzed his tumor by looking closely at RNA, a close chemical cousin of DNA. This would determine whether any of the genes in the tumor were not working as they should. Surprisingly, the researchers found that a normal gene in Wartman’s leukemia cells was producing massive amounts of a protein that likely was fueling the cancer’s growth.

Moreover, they identified a drug approved for advanced kidney cancer that targets this precise genetic error. The drug, Sutent, had never been used to treat patients with acute lymphoblastic leukemia.

Within several weeks of taking the drug, Wartman’s cancer was once again in remission. This allowed him to undergo a second stem cell transplant from an unrelated donor. Today, despite all odds, he remains in remission and is back at work in the laboratory.

Whole-genome sequencing for cancer did not exist when Wartman’s leukemia was first diagnosed. But through the groundbreaking work of Washington University scientists, it has laid the foundation for personalized cancer treatment.

“Until you know what is driving a patients’ cancer, you really don’t have any chance of getting it right,” Ley told the New York Times, in a feature story about Wartman published July 8, 2012. “For the past 40 years, we have been sending generals into battle without a map of the battlefield. What we are doing now is building the map.”
 

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