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?
And after almost a decade of bicoastal collaboration, Emmanuelle Passegu, now a professor in the Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research at the University of California, San Francisco, and Amy Wagers, a professor in Harvard's Department of Stem Cell and Regenerative Biology, have the answer.
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.
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.
"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," Passegu said. This model is a shift from the widely held theory that cancer cells simply crowd out the healthy cells.
Passegu and Wagers stayed in touch, despite the distance between their laboratories, via annual, two-day, "off-the-record" symposiums of junior investigators at the Harvard Stem Cell Institute and
|Contact: B. D. Colen|