Corporate Banner
Satellite Banner
Stem Cells, Cellular Therapy & Biobanking
>
Scientific Community
 
Become a Member | Sign in
Home>News>This Article
  News
Return

Stem Cell Researchers Produce New Model of Leukemia Development

Published: Friday, August 02, 2013
Last Updated: Friday, August 02, 2013
Bookmark and Share
Two former Stanford University postdoctoral fellowsnow have the answer to why patients with leukemia stop producing healthy blood cells.

And after almost a decade of bicoastal collaboration, Emmanuelle Passegué, 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,” Passegué said. This model is a shift from the widely held theory that cancer cells simply crowd out the healthy cells.

Passegué 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 the California Institute for Regenerative Medicine (CIRM). The meetings, which began in 2005 and have continued, require all registrants to keep presentations no longer than 15 minutes and only to discuss unpublished work. “It’s sort of Las Vegas rules,” Wagers said.

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.

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.”

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.


Further Information
Access to this exclusive content is for Technology Networks Premium members only.

Join Technology Networks Premium for free access to:

  • Exclusive articles
  • Presentations from international conferences
  • Over 2,500+ scientific posters on ePosters
  • More than 3,700+ scientific videos on LabTube
  • 35 community eNewsletters


Sign In



Forgotten your details? Click Here
If you are not a member you can join here

*Please note: By logging into TechnologyNetworks.com you agree to accept the use of cookies. To find out more about the cookies we use and how to delete them, see our privacy policy.

Related Content

Zebrafish Reveal Drugs that may Improve Bone Marrow Transplant
Compounds boost stem cell engraftment; could allow more matches for patients with cancer and blood diseases.
Monday, July 27, 2015
Promising Stem Cell Therapy
Animal model of breast-to-brain cancer spread allows testing of therapeutic-cell approach.
Monday, April 27, 2015
Brains or Skin?
Researchers identify a vital protein that can determine head and brain development.
Tuesday, March 17, 2015
Keeping Embryonic Stem Cells in Suspended Animation
Research reveals new strategy to control cellular identity and fate.
Monday, October 27, 2014
Giant Leap Against Diabetes
Ability to produce embryonic stem cells will allow researchers to push faster toward cure.
Friday, October 10, 2014
Improving Cord Blood Transplants
Researchers have published initial results of a Phase Ib human clinical trial of a therapeutic that could improve the success of blood stem cell transplantation.
Tuesday, October 15, 2013
Developing Cancer Drugs
Researchers find therapeutic potential in ‘undruggable’ target.
Wednesday, June 19, 2013
Study uses Stem Cells to Study Variants of Parkinson’s Disease
Personalized medicine closer to reality.
Tuesday, July 17, 2012
Stem Cell Transplant that 'Rebuilds Brain Circuitry'
A brain transplant of stem cells has worked in mice in a breakthrough that signals new hope for conditions from autism to Parkinson’s disease.
Tuesday, November 29, 2011
Helping the Heart Help Itself
An article published in the latest edition of the journal Cell Stem Cell, describes how research by the Harvard Stem Cell Institute points to new use for stem cells.
Wednesday, April 13, 2011
Scientific News
Crucial for Stem Cell Survival Protein Identified Using Editing Tool CRISPR
A team of University of Wisconsin-Madison engineers has identified a protein that is integral to the survival and self-renewal processes of human pluripotent stem cells (hPSC).
A Gene-Sequence Swap Using CRISPR to Cure Haemophilia
For the first time chromosomal defects responsible for hemophilia have been corrected in patient-specific iPSCs using CRISPR-Cas9 nucleases
Access Denied: Leukemia Thwarted by Cutting Off Link to Environmental Support
A new study reveals a protein’s critical – and previously unknown -- role in the development and progression of acute myeloid leukemia (AML), a fast-growing and extremely difficult-to-treat blood cancer.
New Weapon in the Fight Against Blood Cancer
This strategy, which uses patients’ own immune cells, genetically engineered to target tumors, has shown significant success against multiple myeloma, a cancer of the plasma cells that is largely incurable.
Scientists Create CRISPR/Cas9 Knock-In Mutations in Human T Cells
In a project spearheaded by investigators at UC San Francisco, scientists have devised a new strategy to precisely modify human T cells using the genome-editing system known as CRISPR/Cas9.
Zebrafish Reveal Drugs that may Improve Bone Marrow Transplant
Compounds boost stem cell engraftment; could allow more matches for patients with cancer and blood diseases.
New Material Forges the Way for 'Stem Cell Factories'
Researchers have discovered the first fully synthetic substrate with potential to grow billions of stem cells. The researchcould forge the way for the creation of 'stem cell factories' - the mass production of human embryonic (pluripotent) stem cells.
Liver Regrown from Stem Cells
Scientists have repaired a damaged liver in a mouse by transplanting stem cells grown in the laboratory.
Immunotherapy Shows Promise for Myeloma
A strategy, which uses patients’ own immune cells, genetically engineered to target tumors, has shown significant success against multiple myeloma, a cancer of the plasma cells that is largely incurable.
'Google Maps' for the Body
Scientists have revealed research that uses previously top-secret technology to zoom through the human body down to the level of a single cell that could be a game-changer for medicine.
Skyscraper Banner

Skyscraper Banner
Go to LabTube
Go to eposters
 
Access to the latest scientific news
Exclusive articles
Upload and share your posters on ePosters
Latest presentations and webinars
View a library of 1,800+ scientific and medical posters
2,500+ scientific and medical posters
A library of 2,500+ scientific videos on LabTube
3,700+ scientific videos
Close
Premium CrownJOIN TECHNOLOGY NETWORKS PREMIUM FREE!