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St. Jude Children s Research Hospital, University of Pennsylvania

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St. Jude Team Uses Microarrays To Classify Pediatric Leukemia

A team of researchers from St. Jude Children’s Research Hospital in Memphis, Tenn., found that gene-expression profiling may help physicians identify subtypes of pediatric acute lymphoblastic leukemia, and thus customize a treatment strategy.

Pediatric ALL has several subtypes. “Since the subtype may also imply a less favorable prognosis, it is critical to diagnose each individual patient’s subtype so that therapy can be tailored to reduce the chance of a relapse,” the researchers said in a statement.

Today, physicians use ALL subtypes to assign patients to risk groups based on age and gender, white blood-cell count, the presence or absence of leukemia in cerebral spinal fluid, and genetic characteristics of the leukemic cells.

To arrive at their findings, which appear in the Oct. 15 issue of Blood, the official journal of the American Society of Hematology, the St. Jude researchers used Affymetrix HG-U133A and B microarrays to identify gene expression in cell samples obtained from 132 pediatric ALL patients. They found that these cases cluster into seven major subtypes, including the six known prognostic subtypes — BCR-ABL, E2A-PBX1, Hyperdiploid >50, MLL, T-ALL, and TEL-AML1 — and an “other” category. Using the arrays to diagnose and subclassify the 132 ALL cases, the researchers discovered that changes in a cell’s expression profile “vary markedly depending on the genetic lesions that underlie the initiation of the leukemic process.”

“DNA expression profiling allows us to make extremely accurate diagnoses,” James Downing, the senior author of the study, said in the statement. “If microarray technology can be implemented in a cost-effective manner, we may see a day when all leukemia patients undergo expression profiling and then have a unique treatment plan customized for them based on which genes are turned on and which are turned off in his or her leukemia cells.”

“Microarray studies of human leukemia have been at the forefront of efforts to exploit the human genome project to better diagnose and treat cancer, and have set the stage for similar insights into common solid tumors like breast and prostate cancer,” added George Daley, a hematologist at Harvard Medical School.

Downing told SNPtech Reporter that he has been in discussions with several undisclosed drug and diagnostics companies that are interested in licensing his assays.

— KL


Combination of Well-Known Mutations Might Encourage Smoking Cessation

Researchers from the University of Pennsylvania School of Medicine said that smokers with a certain combination of two genetic mutations may more likely abstain from smoking and be less prone to relapsing when trying to quit smoking.

“While previous research has examined the effects of genes related to dopamine, a chemical in the brain associated with reinforcing the effects of nicotine, this study provides the first evidence that genes that alter dopamine function may influence smoking cessation and relapse during treatment,” according to Caryn Lerman, the lead study author and associate director for Cancer Control and Population Science at the Abramson Cancer Center of the University of Pennsylvania.

Lerman and colleagues examined 418 smokers enrolled in a randomized placebo-controlled clinical trial testing the effectiveness of bupropion (marketed as Wellbutrin and Zyban) for smoking cessation. Patients provided blood samples and received bupropion or placebo, and participated in seven sessions of behavioral group counseling. Smoking status, abstinence symptoms, and side effects were recorded weekly, and smoking status was verified at the end of treatment and again at a six-month follow-up session.

Writing in the October issue of Health Psychology, the researchers reported that participants with particular variants of the SLC6A3 dopamine-transporter gene and the DRD2 dopamine-receptor gene displayed “significantly higher abstinences rates” and a “longer time before relapse” than smokers carrying other variants of these genes.

“This gene-gene interaction provides new evidence for the effects of dopamine genes on prospective smoking cessation and underscores the importance of not limiting genetic investigations of smoking behavior to single gene effects,” said Lerman.

Earlier research has linked the same variant of the dopamine transporter gene with higher levels of dopamine in the brain, which “may facilitate smoking cessation.”

“Future smoking cessation studies should evaluate genetic predisposition, as well as the influence of psychological and environmental factors that may promote relapse,” Lerman said.

The study concluded by saying that future studies ought to focus on genetic influences on the pharmacodynamic effects of bupropion.

— KL

 

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