Monday, October 29, 2012 (Last Updated: 10/30/2012)
Huimin Geng, Ph.D., from the Weill Medical College of Cornell University in New York City, and colleagues conducted DNA methylation and gene expression profiling on tumor samples from 215 adults with B-ALL who were participating in a phase III clinical trial, as well as normal control B cells.
The researchers found that, in B-ALL positive for the BCR-ABL1 fusion, aberrant cytosine methylation patterning was associated with overexpression of IL2RA (CD25). The clinical trial showed that CD25 expression was associated with a poor outcome, regardless of BCR-ABL1 status. In B-ALL positive for the E2A-PBX1 fusion, aberrant DNA methylation patterning was associated with direct fusion protein binding. MLL rearrangements were associated with several epigenetic changes, most notably targeting oncogenic BCL6, and blockade or loss of function of BCL6 suppressed proliferation and survival of cells with MLL rearrangements.
"We observed that aberrant epigenetic regulation occurs universally and is distributed to specific gene sets in genetically defined B-ALL subtypes associated with poor outcomes," Geng and colleagues conclude. "We expect these studies to trigger therapeutic trials of BCL6 inhibitors in MLL leukemia and the application of CD25 as a putative biomarker for risk stratification in B-ALLs."
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