Study identifies new prognostic biomarker and therapeutic target for adult B-ALL

Published on October 30, 2012 at 5:33 AM · No Comments

New insight into the aggressive behavior of certain adult B-acute lymphoblastic leukemias has provided researchers with a potential new prognostic biomarker and a promising new therapeutic target.

The research, conducted by Ari Melnick, M.D., associate professor of medicine and director of the Raymond and Beverly Sackler Center for Biomedical and Physical Sciences at Weill Cornell Medical College and a hematologist-oncologist at New York-Presbyterian Hospital/Weill Cornell Medical Center, and colleagues, was published in Cancer Discovery, a journal of the American Association for Cancer Research.

Although B-acute lymphoblastic leukemia is highly curable in children, the disease is usually fatal in adults, and researchers have yet to identify why this is the case. Part of the explanation for the poorer outcomes in adults is the higher frequency of genetic alterations associated with unfavorable prognosis.

In order to better understand why these genetic alterations are associated with poor outcomes, Melnick and colleagues studied 215 diagnostic specimens obtained from adults with B-acute lymphoblastic leukemia who were participating in a large Eastern Cooperative Oncology Group phase III clinical trial.

"We performed an integrative epigenomics study to decode the instructions that determine how these cells behave," Melnick said. "The hope was that this would allow us to identify better survival biomarkers and new therapeutic targets."

In many cancers, genetic alterations work in conjunction with epigenetic changes (changes in the way that DNA is modified and packaged) to promote cancerous behaviors. Looking at the B-acute lymphoblastic leukemia specimens, Melnick and colleagues found that many of the leukemias' bad traits were a result of changes in the epigenetic code. In many cases, the epigenetic changes were directly linked to the proteins generated from the genetic alterations and could be used to identify key master regulators required for the leukemic cells to live, according to Melnick.

"For example, we found that a cell surface molecule called CD25 was an extremely powerful indicator of the presence of the most aggressive and fatal cases," Melnick said.

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