At the second such meeting, Passegu was intrigued by Wagers' cell isolation-based approach to studying the bone marrow niche, the environment where stem cells are found. In the ensuing years, the two scientists swapped protocols, chemical reagents, mice, and even postdoctoral researchers in the pursuit of discovering what causes healthy blood cell dysfunction in leukemia. "Wagers was really involved as a creative spirit in the development of this story," Passegu said.
The observation that leukemia cells can remodel the bone marrow niche parallels work done by HSCI co-director David Scadden of the Harvard-affiliated Massachusetts General Hospital, who demonstrated that particular genetic modifications of bone-forming cells initiate changes in the marrow cavity that suppress normal blood formation and promote the emergence of leukemic cells. "So there's this bidirectional communication that's self-reinforcing, "Wagers said. "And if there's a communication loop like that, you can think about interrupting in many different ways."
Passegu wants to understand how bone-marrow support cells are manipulated to sustain leukemia cells, instead of normal blood cells, in order to design therapies that block these detrimental changes. In the short term, her work could explain why 75 percent of bone marrow transplants are unsuccessful. "A poor niche is likely a very important contributing factor for failure to engraft," she said. Her lab has shown that fibrotic bone marrow conditions can be reversed in as little as a few months by removing the bad-acting maintenance cells, and she is now investigating how to restore the healthy bone marrow environment in leukemia patients.
|Contact: B. D. Colen|