National Cancer Institute Awards Leukemia Reseachers at Siteman $26 Million

The National Cancer Institute, part of the National Institutes of Health (NIH), has awarded two major grants totaling $26 million to leukemia researchers and physicians at the Siteman Cancer

Center at Barnes-Jewish Hospital and Washington University School of Medicine in St. Louis.

The funding helps establish the School of Medicine as a premier center for innovative leukemia research, with a bench-to-beside approach that has the potential to lead to novel therapies that improve survival and reduce treatment-related side effects.

The first award is a five-year, $14.3 million Program Project Grant (PPG) in leukemia. The grant initially was funded at the School of Medicine in 2003 and has been renewed twice. With new support, the scientists aim to identify all the genetic changes underlying the development and progression of acute myeloid leukemia, the most common type of acute leukemia in adults. This information may lead to more personalized treatments for patients based on the unique genetic and molecular signatures of their leukemia cells.

The second award is a prestigious Specialized Program of Research Excellence (SPORE) grant in leukemia. The $11.3 million, five-year award capitalizes on research advances at the medical school to bring new investigational treatments into clinical trials.

“The awards recognize the tremendous scientific depth and breadth of our scientists and clinicians as well as their creativity and commitment to improving treatments for leukemia,” said Daniel Link, MD, the Alan A. and Edith L. Wolff Distinguished Professor of Medicine and principal investigator of the SPORE grant. “Thanks to advances in genomics and molecular biology, we’re on the cusp of a new way of thinking about leukemia and its treatment. There’s a lot to be excited about.”

The two grants bring together several dozen physician scientists and basic scientists who will be involved in a broad portfolio of laboratory and clinical research projects centering on leukemia.

“There’s important synergy between the two grants,” said Timothy Ley, MD, the Lewis T. and Rosalind B. Apple Chair in Oncology and principal investigator of the Program Project Grant. “The PPG focuses on basic research to generate ideas, concepts and technologies that can be evaluated in clinical trials via the SPORE grant.”

More than 20,000 cases of acute leukemia, a cancer of the blood and bone marrow, will be diagnosed in the United States this year, and nearly 12,000 people will die of the disease. While 90 percent of children survive leukemia, the disease is far more deadly in adults.

In recent years, new insights into leukemia and other cancers have been gleaned from pioneering advances at Washington University’s Genome Institute aimed at sequencing the genomes of cancer patients and their tumor cells. This endeavor has given scientists a close look at the mutations that drive the development of cancer.

As part of the new research, scientists in the Division of Oncology will work closely with researchers at The Genome Institute to explore the genetic basis of leukemia in even greater detail.

“Sequencing the genomes of cancer patients enables us to drill down to the level of the DNA in cancer cells to understand how — and why – cancer develops in the first place,” said Richard Wilson, PhD, director of The Genome Institute. “This type of analysis is critical to developing new, improved treatments.”

The SPORE grant supports four new projects that may improve treatments and outcomes for patients with acute leukemia. The projects involve using genomics to predict a patient’s response to chemotherapy, developing novel therapies for acute myeloid leukemia and acute lymphocytic leukemia, and testing a new approach to treating graft-versus-host disease, a potentially deadly complication of stem cell transplants. Clinical trials at the School of Medicine will evaluate the new treatments and therapeutic approaches. Their success would lead to larger clinical studies in cooperation with other institutions.

The SPORE grant also includes a program to train promising young investigators in leukemia research, and funds early-stage, high-risk pilot projects that may transform the way leukemia is diagnosed and treated.

The Program Project Grant involves four laboratory-based projects that target acute myeloid leukemia. About 80 percent of patients with this subtype of leukemia die within five years, when chemotherapy fails to keep the cancer in remission and the disease returns. The new research involves deciphering the genetic rules that govern whether a leukemia patient relapses, developing new ways to predict relapse, determining why some patients develop leukemia after treatment for other cancers, and defining the inherited mutations that dramatically increase the risk of acute myeloid leukemia in some families.

The projects in both grants build on a long history of research advances in leukemia at the School of Medicine, said John DiPersio, MD, PhD, chief of the Division of Oncology and the Virginia E. and Sam J. Golman Professor of Medicine.

“We’re much closer to understanding the genetic origins of the different types of leukemia,” he said. “Now, we can begin to ask what drugs will work best for patients based on the genetic signatures of their cancer cells. But it’s important to conduct careful studies to answer that question so that new treatments are based upon sound science.”

The scientists leading projects and other research cores for the grants are: Timothy Ley, MD, Daniel Link, MD, John DiPersio, MD, PhD, Richard Wilson, PhD, Timothy Graubert, MD, J. Philip Miller, Jackie Payton, MD, PhD, Geoff Uy, MD, Matthew Walter, MD, Mark Watson, MD, PhD, John Welch, MD, PhD, and Peter Westervelt, MD, PhD. Camille Abboud, MD, and Lee Ratner, MD, PhD, will lead the SPORE’s training and development programs.