"We were surprised to see that at high levels, miR-125b induced an aggressive myeloid leukemia in mice," says Caltech graduate student Aadel Chaudhuri, a coauthor on the paper. Myeloid leukemia results when normal blood cellsincluding red blood cells, blood-clotting platelets, and white blood cellsare systematically replaced by abnormal white blood cells that continue to grow uncontrollably, ultimately leading to death if untreated.
"These studies were performed in mice," says Caltech postdoctoral scholar Ryan O'Connell, the lead author of the PNAS paper, "but we also analyzed human blood stem cells and found that the same miRNAs are similarly enriched."
In addition, the researchers found that the expression of that key miRNA enhances the engraftment of human blood stem cells when they are transferred into mouse hosts, "indicating that the expression and function of these miRNAs has been conserved during evolution," O'Connell says.
That means, Chaudhuri says, "it is possible that certain human leukemias could be treated by targeting these newly identified stem-cell microRNAs."
"These findings, when combined with a similar report by physicianscientist David Scadden of the Massachusetts General Hospital and the Harvard Stem Cell Institute, show that miRNAs are important molecules that control the function of blood stem cells," he says. "These observations have important implications for both the diagnosis and treatment of cancer and anemia, which arise from defective blood stem cells. Blood stem cell transplantations have become a common form of therapy to treat cancer, autoimmunity, and even certain types of infectious diseases, and the exploitation of miRNA expression levels in blood stem cells through therapeutic targeting could be used to augment this approach."
"These two studies add
|Contact: Kathy Svitil|
California Institute of Technology