The St. Jude Children's Research Hospital--Washington University Pediatric Cancer Genome Project reports that a highly aggressive form of leukemia in infants has surprisingly few mutations beyond the chromosomal rearrangement that affects the MLL gene. The findings suggest that targeting the alteration is likely the key to improved survival. The research was published online on March 2, 2015 in Nature Genetics. The study is the most comprehensive analysis yet of this rare, but aggressive subtype of pediatric acute lymphoblastic leukemia (ALL) that occurs during the first year of life and is sometimes diagnosed at birth. The leukemia cells of up to 80 percent of infants with ALL have a chromosomal rearrangement that fuses the MLL gene to a gene on a different chromosome. The resulting MLL fusion gene encodes an abnormal protein. The fusion protein plays a key role in transforming normal blood cells into leukemia cells. Researchers used whole genome sequencing and other techniques to identify the genetic alterations in 65 infants with ALL, including 47 with the MLL rearrangement. Scientists were surprised to find that despite being an aggressive leukemia, the MLL rearranged subtype had among the lowest mutation rates reported for any cancer. "These results show that to improve survival for patients with this aggressive leukemia, we need to develop drugs that target the abnormal proteins produced by the MLL fusion gene or that interact with the abnormal MLL fusion protein to shut down the cellular machinery that drives their tumors," said senior and co-corresponding author James R. Downing, M.D., St. Jude President and CEO. "That will not be easy, but this study found no obvious cooperating mutations to target."
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