Adult Lymphoblastic Leukemia Diagnostic and Therapeutic Markers Identified

Cancer researchers have identified a new biomarker for adult B-cell precursor acute lymphoblastic leukemia (B-ALL) and pinpointed a gene required for cancer proliferation and survival as a target for directed therapeutic treatment.

Investigators at Weill Cornell Medical College (New York, NY, USA) conducted DNA methylation and gene expression profiling on a cohort of 215 adult patients with B-ALL enrolled in a single phase III clinical trial and normal control B cells.

They reported in the October 29, 2012, online edition of the journal Cancer Discovery that epigenetic change in leukemia cell DNA due to aberrant cytosine methylation patterning was centered on a cytokine network defined by hypomethylation and overexpression of IL2RA (CD25 - the alpha chain of the IL-2 receptor). Data from the clinical trial showed that CD25 expression was strongly associated with a poor outcome in patients with B-ALL, suggesting CD25 as a novel prognostic biomarker for the disease.

Further findings obtained during the study revealed that blockade or loss of function of the BCL6 oncogene suppressed proliferation and survival of leukemia cells, suggesting that BCL6-targeted therapy could be a productive new therapeutic strategy for treating B-ALLs.

"We performed an integrative epigenomics study to decode the instructions that determine how these cells behave," said senior author Dr. Ari Melnick, associate professor of medicine at Weill Cornell Medical College. "The hope was that this would allow us to identify better survival biomarkers and new therapeutic targets. We then designed inhibitors of BCL6 and showed that we could kill leukemia cells from patients enrolled in the clinical trial by blocking its function."

"These results will ultimately lead to biomarkers that help guide treatment and to the development of therapies that will be more effective for patients with this aggressive form of leukemia," said Dr. 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."

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