May 1, 2013 A team of researchers led by Washington University School of Medicine in St. Louis has identified virtually all of the major mutations that drive acute myeloid leukemia (AML), a fast-growing blood cancer in adults that often is difficult to treat.

The findings, published online May 1 in The New England Journal of Medicine, pave the way for developing better treatments for AML based on the genetic profile of a patient's cancer. They also could lead to ways to more accurately predict the severity of disease in individual patients.

"We now have a genetic playbook for this type of leukemia," says study co-leader Timothy Ley, MD, associate director for cancer genomics at The Genome Institute at Washington University School of Medicine. "We don't know all the rules yet, but we know all the major players. This information can help us begin to understand which patients need more aggressive treatment right up front and which can be treated effectively with standard chemotherapy."

Some 200 patients newly diagnosed with AML were involved in the study, funded by the National Institutes of Health (NIH) as part of The Cancer Genome Atlas project. Nearly 150 researchers were involved in the effort.

A second Cancer Genome Atlas paper will be published May 2 in Nature. That research, also led by Washington University, shows that adding genomics-based testing to the standard diagnostic workup could change the recommended course of treatment for some women.

The scientists sequenced the DNA of each patient's leukemia cells and compared the data to DNA from that same patient's healthy cells. In this way, they found the mutations that only occurred in the cancer cells and contributed to the development and progression of AML in each patient. They also looked for defects in RNA (a close chemical cousin of DNA) and other changes that alter the expression of genes without actually changing the DNA.

"These results provide important new insights into the genomics of a deadly and difficult-to-treat cancer, and underscore the power and scope of The Cancer Genome Atlas project," says NIH Director Francis S. Collins, MD, PhD.

Compared to other adult cancers, AML is caused by relatively few mutations, the new study shows. Cancer cells in the AML patients had an average of 13 mutated genes, far fewer than the several hundred typically found in breast, lung and other solid tumors.

By studying a large number of AML cases, the scientists predict they have found nearly all of the major mutations that occur in patients with the disease.

"If only 5 percent of AML cases have a particular gene that is mutated, there is a greater than 99 percent chance that we encountered that mutation at least once in this study," says co-leader Richard K. Wilson, PhD, director of Washington University's Genome Institute. "There are still rare mutations that remain to be discovered, but we expect they will fall into the same genetic pathways or gene sets that we identified as being very strongly associated with AML."

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Scientists assemble genetic playbook for acute leukemia

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