Multiple myeloma survival down with high ADAR1 RNA expression
Noting that ADAR1 occurs in 30 to 50 percent of MM patients and portends a poor prognosis, Elisa Lazzari, Ph.D., from the University of California in San Diego, and colleagues examined the role of genomic amplification combined with inflammatory cytokine activation of ADAR1.
The researchers report that there was a correlation between high ADAR1 RNA expression with reduced patient survival rates in the Multiple Myeloma Research Foundation CoMMpass data set. Alu-dependent editing and transcriptional activity of GLI1, a Hedgehog pathway transcriptional activator and self-renewal agonist, was enhanced by expression of wild-type, but not mutant ADAR1; expression also promoted immunomodulatory drug resistance in vitro. In serially transplantable patient-derived xenografts, ADAR1 knockdown reduced regeneration of high-risk MM.
"These data demonstrate that ADAR1 promotes malignant regeneration of MM and if selectively inhibited may obviate progression and relapse," the authors write.
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