Sylvester Researchers Play Key Role in Groundbreaking AML Study

Sylvester Comprehensive Cancer Center is one of 11 academic medical centers collaborating in the Beat AML initiative, sponsored by the Leukemia & Lymphoma Society.

Microscopic view of acute myeloid leukemia cells.

For more than five years, samples from 526 patients were collected from across the country. The study, “Functional Genomic Landscape of Acute Myeloid Leukemia,” was published on October 17 in Nature.

“This is the largest study to date to analyze at a very deep genetic level individual patient leukemia samples to better understand how to treat this devastating disease that has few approved treatment options,” explained Justin Watts, M.D., the lead investigator at Sylvester.

Oregon Health & Science University Knight Cancer Institute Director Brian Druker, M.D., led this multi-center study. Four Sylvester researchers, including Dr. Watts, were co-authors and made important contributions to this seminal study, including collecting 138 bone marrow samples and complex clinical data on 62 unique AML patients over a two-year period.

“We are thrilled that Sylvester was one of the largest participants in this groundbreaking trial conducted across the United States,” said Sylvester Director Stephen D. Nimer, M.D.

“The study illustrates the commitment of our investigators, research staff, and most importantly our patients to advancing the most leading-edge leukemia research in the world at Sylvester, and we were honored to participate,” said Dr. Watts.

Comprehensive genomic profiling and analysis was done on all of the patients’ tumors. In addition, the study added functional profiling (drug sensitivity screening), which means it tested each patient’s leukemia cells against a host of targeted cancer therapies in the lab, to see which drugs were the most active in each patient.

This was then integrated with the genetic data (whole exome and RNA sequencing), to suggest new avenues of treatment for mutationally defined cohorts of AML patients, including patients with unique combinations of mutations, as well as for patients with certain gene expression profiles without a clear targetable mutation.

“Hundreds of patients were tested against hundreds of potential therapies, and by doing so it became clear which mutations increase and which mutations decrease the sensitivity of cancer cells to a specific form of therapy. Also, which combinations of mutations create a unique sensitivity to therapy. This study conducted in patients with AML will hopefully be replicated in other cancers in the future,” said Dr. Nimer.

All of this information greatly advances our understanding of disease biology, precision medicine, and targeted therapy for AML, and it is also publicly available at the interactive website Vizome.org, which promises to be a huge resource for leukemia and genomics researchers for years to come.