Investigators from Washington University Siteman Cancer Center at Barnes-Jewish Hospital and Washington University Medical Center in St. Louis, MO, have been awarded a $15 million grant to enable them to continue ongoing study the genetic changes that drive acute myeloid leukemia (AML), a deadly blood cancer, and in the process, develop methods to predict patients’ response to therapy. It is hoped that in the future these findings will support investigators to develop superior precision therapies: tailored to patients based on the genetic characteristics of their cancer cells. This group represents one of the most elite AML research hubs worldwide.
Genomics of AML
The team is funded by what is known as a “program project grant” supporting integrated research projects covering one type of cancer. In this case known as “Genomics of AML,” it was originally awarded to the same group of investigators back in 2003 and this has been renewed three times. It is the only program project grant focused on AML in the United States. The team is committed to the ongoing analysis of how tumors respond and evolve during therapy in the quest to nail the treatment that kills that returning cancer.
The Scientists in St. Louis Produce Results
The team continues to secure funds as they make progress, step by step, at giving society a better understanding of AML. For example, the funding enabled the group to sequence the first human cancer genomes (from AML patients) in 2008 and 2009 supporting the entire cancer genomics field.
The St. Louis-based team have contributed a great amount of knowledge to the quest to develop therapies for leukemia. It starts with research at the cellular level. For example, the team’s research has established that even in the bone marrow of a single patient, leukemia cells are not identical. In fact, they reveal that cancerous cells are also a moving target—evolving and adapting to different treatment strategies. The team now understands that although a treatment might destroy many AML cells, a subset of cells may result containing different sets of mutations—hence leading to expansion and relapse.
In 2018 the School of Medicine received $11.5 million for a Specialized Program of Research Excellence (SPORE) grant, establishing Washington University as a nexus for innovative leukemia research and leadership in establishing new leukemia therapies.
Even if the care team can achieve remission, the cancer most often returns. The five-year survival rate is 28%—lower for older patients.
The New Grant & The Focus
The Washington University investigative team now known that mutations in a patient’s AML cells can help them predict the aggressiveness of the leukemia and response to treatment. With the new funds, the St. Louis investigators will pursue a deeper and richer understanding of why some patients relapse and why some don’t via a study of the interplay of mutations and gene expression patterns that they alter.
Four Projects Supported by Grant
The grant supports four projects for the St. Louis-based group including:
- Led by Dr. Ley, they will examine the genetic and epigenetic characteristics of intermediate-risk AML—the most common type. Also the most difficult type to predict how well patients will do post standard therapy. The ultimate goal of this project is to further uncover better relapse predictors.
- Dr. John F. DiPersio MD, PhD, Virginia E. and Sam J. Golman Professor of Medicine, and Michael P. Rettig, PhD, an associate professor of medicine, the second project examines ways to improve patient responses to stem cell transplantation with an emphasis on ways to boost the way the transplanted immune cells attack the patients’ AML.
- The third project, led by Matthew J. Walter, MD, a professor of medicine focuses on the genetics and epigenetics of a different but closely related disease called myelodysplastic syndrome (MDS) that is slow-growing but sometimes progresses to AML. They seek to better understand why some patients progress to AML and find ways to prevent this.
- The fourth project is led by Daniel C. Link, MD, the Alan A. and Edith L. Wolff Professor of Medicine, and focuses on the study and better understanding of the genetic and epigenetic changes in an important gene called TP53, which often drives AML and has an impact on patient prognosis.
Principal Investigator Comment
Timothy J. Ley, MD, Lewis T. and Rosalind B. Apple, Professor of Medicine, reports that the grant will support the team in this progression of precision diagnosis, analysis, and treatment stating. “This grant is having a direct impact on how we approach patients.” Dr. Ley continued, “Today, every single patient with AML who comes to Siteman gets some kind of genetic analysis for their cancer. The mutations in their leukemia cells help physicians select the best treatment option.”
Timothy J. Ley, MD, Lewis T. and Rosalind B. Apple Professor of Medicine
Dr. John F. DiPersio, MD, PhD, Virginia E. and Sam J. Golman Professor of Medicine
Matthew J. Walter, MD, a professor of medicine
Michael P. Rettig, PhD, associate professor of medicine
Daniel C. Link, MD, the Alan A. and Edith L. Wolff Professor of Medicine
Call to Action: Do you or a loved one have a diagnosis of AML? Washington University St. Louis Siteman Cancer Center is one of the top hubs of research activity in the world. Why not contact the institution to learn more about a second opinion or participating in research, if there is an opportunity to do so? Interested in the science behind the team’s research? Connect with the institution to explore partnerships.