Altered expression of genes - either turned on or off abnormally - is a hallmark of cancer. Researchers have now found that differences in the expression of a relatively small number of genes indicate whether childhood acute lymphoblastic leukemia (ALL) is resistant or susceptible to the drugs commonly used to treat the condition.

“Up until now, we’ve gotten an 80 percent cure rate for patients with ALL by a lot of smart empiricism,” senior investigator Dr. William E. Evans told Reuters Health. “This new research represents one of several new strategies being used to bring modern technology of the human genome to bear on the last 20 percent of children who are not being cured.”

“Essentially,” he continued, “we took a genome-wide approach to ask the question, what are the differences in leukemia cells of patients whose cells are resistant to…drugs versus those that are sensitive?”

Evans, at St. Jude Children’s Research Hospital in Memphis, Tennessee, and his team tested leukemia cells from 173 newly diagnosed children for susceptibility to several chemotherapy drugs. About 23 percent of the children had relapsed after treatment.

As they report in this week’s New England Journal of Medicine, the investigator found 124 unique genes that were expressed differently in sensitive and resistant cells. From this information they developed a drug-resistance gene-expression score.

When Evans’ group applied this to another group of 98 children with ALL, a high score was associated with an 11-fold higher probability of relapse compared with a low score.

In the near future, Evans suggested, physicians may routinely perform gene expression profiling on patients newly diagnosed with ALL. “If a patient has a signature suggesting resistance to drug A, maybe we should focus on drugs B, C and D, and downplay drug A,” he said.

In addition, “we’ve identified 152 potential new drug targets” that may be used to find new drugs to convert resistant leukemia cells to sensitive leukemia cells, he added. These drugs “may not be anti-leukemic per se, but rather drugs to modulate sensitivity of leukemia cells to existing anti-leukemia drugs.”

His group has placed this gene data in a publicly available database “so that anyone who wants to download and analyze it further can do that,” he said.

SOURCE: New England Journal of Medicine, August 5, 2004.