Main Category: Lymphoma / Leukemia / Myeloma
Also Included In: Stem Cell Research
Article Date: 02 Aug 2013 – 1:00 PDT
At the second such meeting, Passegué 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,” Passegué said.
They have found that cancer stem cells actively remodel the environment of the bone marrow, where blood cells are formed, so that it is hospitable only to diseased cells. This finding could influence the effectiveness of bone marrow transplants, currently the only cure for late-stage leukemia, but with a 25 percent success rate due to repopulation of residual cancer cells.
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Passegué 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.
Eight years ago, two former Stanford University postdoctoral fellows, one of them still in California and the other at the Harvard Stem Cell Institute (HSCI) in Cambridge, began exchanging theories about why patients with leukemia stop producing healthy blood cells. What was it, they asked, that caused bone marrow to stop producing normal blood-producing cells?
University, Harvard. “Stem cell researchers produce new model of leukemia development.” Medical News Today. MediLexicon, Intl., 2 Aug. 2013. Web.
2 Aug. 2013. <http://www.medicalnewstoday.com/releases/264220.php>
Koen Schepers, now at the University Medical Center Utrecht, was the first author on this study. The work was supported by the National Institutes of Health, CIRM, a NWO Rubicon Fellowship, and a KWF Fellowship.
“They remodel the microenvironment so that it is basically callous, kicking the normal stem cells out of the bone marrow and encouraging the production of even more leukemic cells,” Passegué said. This model is a shift from the widely held theory that cancer cells simply crowd out the healthy cells.
Harvard University
Their results, which were recently published online in Cell Stem Cell, show that leukemia cells cannot replicate in the bone marrow niche as well as healthy blood-forming stem cells can, so the cancer cells gain the advantage by triggering bone marrow-maintenance cells to deposit collagen and inflammatory proteins, leading to fibrosis – or scarring – of the bone marrow cavity.
Passegué and Wagers believe the success of this research reflects the value of scientific partnerships. “Both HSCI and CIRM understand the importance of fostering the open communication and collaboration that drives innovation in science,” Wagers said.
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