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International Team Uses Microarrays to Identify Aggressive AML; Is Dx Far Off?

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A team of scientists at the Stanford University School of Medicine claims to have identified 133 genes that apparently are associated with highly aggressive forms of adult acute myeloid leukemia.

If verified, the researchers’ findings may lead to a molecular diagnostic that could help oncologists fine-tune treatments for this common acute form of leukemia.

“This intermediate-risk group poses the biggest problem for assigning treatment,” Jonathan Pollack, assistant professor of pathology, who led the study, said in a statement last week.

For instance, aggressive forms of AML are known to relapse following chemotherapy, so oncologists are eager for more efficacious — and safer — treatment options for their patients. Cutting-edge treatments such as stem cell transplants “are considered too risky for patients with less aggressive forms of the disease,” the researcher explained in the statement.

To arrive at their results, which appear in the April 15 New England Journal of Medicine, Pollack and colleagues in Germany collected tumor samples from 116 adults with AML, which included 45 with an intermediate-risk form of the disease. The researchers used microarrays to determine expression levels from 26,260 genes in each sample.

The team was able to find two distinct patterns of genes that are either under-expressed or over-expressed. “These patterns correlated with how long the intermediate-risk patients lived after diagnosis,” the scientists said. Patients in the first group lived on average about twice as long as those in the second group, which had in common 133 genes.

“You don’t see a difference between these cancers under a microscope, but when you look at gene expression they are quite distinct,” Pollack said in the statement.

It is this kind of information that Pollack claims may be able to help physicians make better treatment decisions. Moreover, said Pollack, some of the over-expressed genes are not known to be involved in AML.

“Studying these genes and their proteins could lead to new treatments for the disease,” Pollack said.

“This kind of study can benefit patients in the short term, especially in matching treatments to individuals,” Pollack said.

That’s in contrast to developing new drugs, a process that can take up to 15 years to reach patients. In order for gene activity to become widely used for choosing treatments, Pollack said the results first must be independently replicated and researchers must find the smallest number of genes that can still discriminate between treatment groups.

However, a molecular diagnostic based on these data may be take years. Speaking with Pharmacogenomics Reporter last week, Pollack said his group’s “number one goal” is to replicate the findings by studying a much larger and independent cohort of patients with AML.

“Once we do that I think the next goal will be to try to see whether the test actually does a better job than currently used markers — mainly, cytogenetics — in stratifying patients for treatment,” he said. He added that this validating study is currently underway at Stanford, and he expects results to be published “within the year.”

Pollock also said that the 133-gene group “is a little bit too much” for what hospital-based clinical labs are typically capable of handling. Consequently, he said that another goal of the team is to “try to reduce the number of genes to a much smaller and more manageable set of genes that performs equally well.”

—KL


Austrian Team Said DNA Methylation in Stool May Help Predict Colorectal Cancer

A researcher in Austria said he has used microarray technology to detect DNA methylation in stool samples — a technique that may enable physicians to better detect the presence of colorectal cancer.

The results of the study, if affirmed, may lead to a molecular diagnostic test for the disease based on the methylation profile of a single gene.

To arrive at their results, researchers led by Hannes M ller from the Medical University Innsbruck, used a PCR assay to identify DNA changes in stool from patients with the disease and from controls “to assess the most promising DNA methylation markers from a long list of candidate genes,” they wrote in this week’s issue of the Lancet. Then, they tested for these potential markers in samples from 49 individuals culled from patients and controls.

They found that the SFRP2 gene was methylated “more frequently” in DNA from the stools of patients with colorectal cancer than in samples from controls. M ller said the results have a sensitivity of between 77 percent and 90 percent, and specificity of around 77 percent.“

SFRP2 methylation could, therefore, be useful as a marker in screening for colorectal cancer,” the researchers wrote in the statement.

“To our knowledge, SFRP2 methylation represents one of the most sensitive markers for identifying colorectal cancer, besides mutation analysis and protein analysis, in stool samples,” Martin Widschwendter, a professor of medicine at the Medical University Innsbruck, and the principle investigator of this study, wrote. “Whether a panel of genetic and epigenetic markers in stool could be used to identify colorectal cancer at an early stage remains to be shown.”

—KL

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