Furthermore, the researchers also discovered changes that might explain why the gene is overactive. For example, they found that proteins called histones, which help control a gene's activity, were being altered.
"We show that the histones are being modified in ways that can increase the activity of the HoxA9 gene," says first author Adrienne M. Dorrance, a graduate student in Caligiuri's laboratory and the recipient of the Lady Tata Memorial Trust Award for her work on this gene. "We believe that the mutation is somehow activating this modification."
In spite of these changes, the mouse strain does not develop leukemia.
"The failure of the mice to develop leukemia suggests that the partial tandem duplication occurs early in the leukemic process and that additional mutations are needed for the disease to occur," Dorrance says. "That's what we're now focused on."
"Ultimately," Caligiuri says, "we believe that this mouse will further our understanding of how leukemia develops and open up new therapeutic options for this group of AML patients with a poor prognosis."