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Three Molecular Triggers Threaten Leukemia Patients

The road to better treatment for the most common form of adult leukemia will require blocking multiple molecular pathways that fuel the disease//, researchers at The University of Texas M. D. Anderson Cancer Center report in the Oct. 1 edition of the journal Blood.

The research team examined blood and bone marrow samples of 188 adults with acute myelogenous leukemia (AML) and then followed the patients' progress to gauge the cumulative impact of a trio of cell-signaling chain reactions on the disease.

"We found that the more of these pathways that are active in a patient, the worse their prognosis," says first author Steve Kornblau, M.D., associate professor in the Department of Blood and Marrow Transplantation.

Patients who had none of the three molecular cascades active had a median survival time of 78.6 weeks. For those with one highly active pathway, median survival was 57.9 weeks. With two, it was 42.3 weeks. Patients with high activation of all three pathways had a median survival time of just 23.4 weeks.

"Targeting just one of these pathways won't be effective because we also found that they cross-activate each other, they essentially cover for each other," Kornblau said. "New therapies will have to target multiple pathways to be effective."

This presents several challenges to discovering a successful treatment for AML, the research team noted. New drugs are typically evaluated individually during development, so a medication that blocks one of these pathways is likely to fail to treat AML by itself. It would probably be discarded as a single therapy when it could become part of a multiple-drug attack on the disease.

Finding a multi-drug therapy also will require an unprecedented degree of cooperation among pharmaceutical firms and academic investigators holding the rights to different agents that are active in different molecular pathways, Kornblau and colleagues noted.

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