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Comprehensive Look at Rare Leukemia Finds Relatively Few Genetic Changes Launch Disease
Date:7/27/2009

e genome of childhood AML and take a more detailed look at particular AML subtypes.

Added Ina Radtke, Ph.D., the paper's lead author: "This rigorous systemic genome-wide study was an important step to direct our future efforts to the most effective strategies to pinpoint lesions in AML." She is a postdoctoral fellow in Downing's laboratory.

For this study, researchers analyzed leukemia cells from 111 St. Jude AML patients representing the seven most common subtypes of the disease. The scientists used several techniques to catalog the changes, including single-nucleotide-polymorphism (SNPs) microarrays to chart genome-wide regions of DNA gain or loss, which are known as copy number alterations (CNAs). To identify point mutations, the researchers also performed DNA re-sequencing of 25 genes that are commonly mutated in adult AML. Point mutations involve a single chemical change in the molecular building blocks of DNA.

The data demonstrated that, in contrast to pediatric acute lymphoblastic leukemia (ALL), AML is characterized by a very low burden of mutations. The researchers found slightly more than two CNAs per AML patient, and less than one point mutation per patient in the genes sequenced. The scientists also reported just 21 percent of AML patients had six or more lesions. By comparison, an earlier St. Jude study reported 77 percent of young ALL patients, a more common cancer, had that much DNA damage. Even more surprising, 34 percent of patients in this study lacked any apparent CNA, and 28 percent of those with a translocation lacked additional DNA abnormalities. Certain chromosomal re-arrangements are known as translocations.

The investigators also found no association between CNAs and patient outcome. Despite the low overall number of lesions in the patients studied, novel recurring regions of genetic alteration were identified that harbor known and potential new cancer genes.


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SOURCE St. Jude Children's Research Hospital
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