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Cancer sequencing project identifies potential approaches to combat aggressive leukemia
Date:1/11/2012

UNX1, IKZF1 and GATA3. GATA3 helps regulate the early stages of T cell development, and mutations in the gene were found exclusively in ETP-ALL patients.

Epigenetic mutations, which are alterations affecting genes that indirectly influence the activity of other genes, were also more common in ETP-ALL patients. These genes, including EZH2 and SUZ12, were mutated or deleted in 45 percent of ETP-ALL patients, but in just 11 percent of the comparison group. The targeted genes modify proteins known as histones, which control gene activity through DNA binding.

Researchers also showed that ETP-ALL includes recurring mutations in about a half-dozen genes not previously linked to blood cancers. The list includes the genes RELN and DNM2. "The pattern of mutations we found in those genes suggests they function as tumor suppressors and their loss contributes to the malignant transformation of developing blood cells," Mullighan said.

Mullighan said work is underway to develop laboratory models of human ETP-ALL and to use these models to identify AML drugs that are most likely to benefit ETP-ALL patients. The list of possible drugs includes high-dose cytarabine and targeted chemotherapy agents that inhibit activity in the cytokine receptor and JAK signaling pathways found in this study to be disrupted in ETP-ALL patients, researchers said. Those pathways help regulate cell division and normal development of the blood system.

"This is the first of a series of important discoveries on the genomic basis of childhood cancers that are emerging from the Pediatric Cancer Genome Project, which is on schedule to fully sequence 600 pediatric cancer genomes by 2013," said Dr. William E. Evans, St. Jude director and CEO. James Downing, M.D., St. Jude scientific director, St. Jude PCGP site leader and a corresponding author of the study, added: "This study highlights how the genome project is generating new insights into the genetic alterations that underl
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Contact: Carrie Strehlau
media@stjude.org
901-595-2295
St. Jude Children's Research Hospital
Source:Eurekalert

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