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Epigenetic pathway and new drug show promise in reversing a hard-to-treat childhood cancer
Date:7/11/2011

A difficult-to-treat form of childhood leukemia relies on changes in the structure of DNA so-called epigenetic changes to wreak genomic havoc within white blood cells, according to one of two studies conducted by a research team at Children's Hospital Boston and Dana-Farber Cancer Institute. Together with collaborators from a biotechnology company, the same team also showed that a new drug that blocks these changes could deactivate cancer-promoting genes and halt the growth of this cancer.

These studies, reported in a pair of papers in the July 11, 2011 issue of Cancer Cell, are the first to therapeutically target a core epigenetic vulnerability in the subgroup of leukemias caused by a "reshuffling" or rearrangement of the mixed lineage leukemia (MLL) gene.

"We have known for a while that MLL leukemias arise from widespread alterations not in the genetic code itself, but in the structure of the DNA and the proteins associated with it," according to Scott Armstrong, MD, PhD, a pediatric oncologist at Children's and Dana-Farber. "We now show that these epigenetic changes indeed turn on cancer-promoting genes within white blood cells, and ultimately cause the leukemia.

"Even more importantly," he continued, "we show that we can reverse the process."

While childhood leukemia is one of the great success stories in cancer therapy, those caused by MLL gene rearrangements stand out as devastating exceptions. In these cancers, a portion of chromosome 11 (where the MLL gene resides) breaks off and fuses with parts of other chromosomes to create new fusion proteins. The fusion proteins subvert the normal function of the MLL gene and activate a set of leukemia-causing genes.

MLL gene rearrangements account for approximately 10 percent of children and adults diagnosed with acute lymphoblastic or acute myeloid leukemias; most of these patients do not respond well to standard leukemia treatments.

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Contact: Rob Graham
Rob.Graham@childrens.harvard.edu
617-919-3110
Children's Hospital Boston
Source:Eurekalert

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