Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

URMC Finds Leukemia Cells Are “Bad to the Bone”

27.01.2012
University of Rochester Medical Center researchers have discovered new links between leukemia cells and cells involved in bone formation, offering a fresh perspective on how the blood cancer progresses and raising the possibility that therapies for bone disorders could help in the treatment of leukemia.

The research, led by graduate student Benjamin J. Frisch in the James P. Wilmot Cancer Center laboratory of corresponding author Laura M. Calvi, M.D., is featured in the journal Blood. It is accompanied by an editorial – “Bad to the Bone” -- written by another leading investigator in the field, Steven W. Lane, M.D., of Queensland Institute of Medical Research. Lane says that the URMC’s unexpected laboratory finding provokes new clinical questions, such as whether screening for osteoporosis could provide any useful information for how to manage acute leukemia in newly diagnosed patients.

Leukemia is a devastating disease that results in the disruption of normal blood production. Blood stem cells (hematopoietic stem cells or HSCs) give rise to all mature blood cells and maintain a balance of self-renewal and expansion. However, in this study, even when leukemia is barely traceable in the blood, leukemic cells implant in the bone marrow and attack the body’s natural process of making healthy blood stem cells.

In this hematopoietic microenvironment, or niche, investigators have been searching for clues. In 2003 Calvi introduced the concept that osteoblasts, which actively work to form bone in this same microenvironment, might have a key role in expanding and supporting the production of normal blood cells. Published in the journal Nature, that study served as the basis for the current investigation.

Frisch began focusing on the impact of the leukemia cells, which reside on the inside surface of bones adjacent to bone marrow activity. Until now, according to the Blood paper, no one had defined the important interactions that take place between leukemia cells and osteoblasts (bone forming cells) and osteoclasts, which continually break down bone. Frisch and colleagues used a mouse model and human leukemia tissue samples to show that:
The way in which leukemia alters the balance and cycles of osteoblast and osteoclast activity is complex and counterintuitive, and results in several measurable changes to the skeleton.

For example, since bone formation and bone resorption are usually tightly knit functions, researchers expected to see that dramatic bone loss due to leukemia would also be consistent with a breakdown of bone and minerals, or resorption. Instead, they saw a mild increase in osteoclastic cells responsible for bone resorption, suggesting that leukemia uncouples these two bone cell functions. Ultimately, researchers would like to understand more about osteoclasts during the disease process, so that they can perhaps target those cells for treatment.

In this study, leukemia caused low-level and widespread bone thinning and bone loss, similar to osteoporosis, particularly in the long bones. Preliminary lab experiments showed that treatment with bisphosphonates, a commonly used class of drugs for people who suffer from bone loss, partially restored bone loss in mice with leukemia.

Leukemia results in the expression of a protein, known as CCL3, which slows bone formation. Thus, elevated CCL3 levels in leukemia make it a tempting treatment target. Theoretically, newer drugs that block the CCL3 pathway might be able to restore the low-level, net loss of bone observed in many leukemia patients. A few drug compounds that act on the CCL3 pathway are under study in early-stage clinical trials, Frisch said.

Another interesting question, the study noted, is the way in which dysfunction in the bone marrow microenvironment might delay a patient’s recovery after chemotherapy, or be the catalyst for relapse.

“Our findings are quite provocative and we hope they will lead to new approaches to promote normal blood production in patients with blood cancers,” said Calvi, associate professor of Medicine. “Because the loss of normal hematopoietic function is the chief cause of serious illness and death among leukemia patients, it is critical that we understand all aspects of how this occurs and find new strategies to accelerate the recovery of these defects.”

Funding was provided by the Wilmot Scholar Cancer Research Award and the Pew Scholar in Biomedical Sciences Award. Co-authors include John M. Ashton, Ph.D., URMC Department of Genetics; Lianping Xing, Ph.D., URMC Department of Pathology and Laboratory Medicine; Michael W. Becker, M.D., URMC Department of Medicine, and Craig T. Jordan, Ph.D., the Philip and Marilyn Wehrheim Professor of Medicine at Wilmot.

For Media Inquiries:
Leslie Orr
(585) 275-5774
Email Leslie Orr

Leslie Orr | EurekAlert!
Further information:
http://www.urmc.rochester.edu

More articles from Health and Medicine:

nachricht Unique brain 'fingerprint' can predict drug effectiveness
11.07.2018 | McGill University

nachricht Direct conversion of non-neuronal cells into nerve cells
03.07.2018 | Universitätsmedizin der Johannes Gutenberg-Universität Mainz

All articles from Health and Medicine >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: First evidence on the source of extragalactic particles

For the first time ever, scientists have determined the cosmic origin of highest-energy neutrinos. A research group led by IceCube scientist Elisa Resconi, spokesperson of the Collaborative Research Center SFB1258 at the Technical University of Munich (TUM), provides an important piece of evidence that the particles detected by the IceCube neutrino telescope at the South Pole originate from a galaxy four billion light-years away from Earth.

To rule out other origins with certainty, the team led by neutrino physicist Elisa Resconi from the Technical University of Munich and multi-wavelength...

Im Focus: Magnetic vortices: Two independent magnetic skyrmion phases discovered in a single material

For the first time a team of researchers have discovered two different phases of magnetic skyrmions in a single material. Physicists of the Technical Universities of Munich and Dresden and the University of Cologne can now better study and understand the properties of these magnetic structures, which are important for both basic research and applications.

Whirlpools are an everyday experience in a bath tub: When the water is drained a circular vortex is formed. Typically, such whirls are rather stable. Similar...

Im Focus: Breaking the bond: To take part or not?

Physicists working with Roland Wester at the University of Innsbruck have investigated if and how chemical reactions can be influenced by targeted vibrational excitation of the reactants. They were able to demonstrate that excitation with a laser beam does not affect the efficiency of a chemical exchange reaction and that the excited molecular group acts only as a spectator in the reaction.

A frequently used reaction in organic chemistry is nucleophilic substitution. It plays, for example, an important role in in the synthesis of new chemical...

Im Focus: New 2D Spectroscopy Methods

Optical spectroscopy allows investigating the energy structure and dynamic properties of complex quantum systems. Researchers from the University of Würzburg present two new approaches of coherent two-dimensional spectroscopy.

"Put an excitation into the system and observe how it evolves." According to physicist Professor Tobias Brixner, this is the credo of optical spectroscopy....

Im Focus: Chemical reactions in the light of ultrashort X-ray pulses from free-electron lasers

Ultra-short, high-intensity X-ray flashes open the door to the foundations of chemical reactions. Free-electron lasers generate these kinds of pulses, but there is a catch: the pulses vary in duration and energy. An international research team has now presented a solution: Using a ring of 16 detectors and a circularly polarized laser beam, they can determine both factors with attosecond accuracy.

Free-electron lasers (FELs) generate extremely short and intense X-ray flashes. Researchers can use these flashes to resolve structures with diameters on the...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

Leading experts in Diabetes, Metabolism and Biomedical Engineering discuss Precision Medicine

13.07.2018 | Event News

Conference on Laser Polishing – LaP: Fine Tuning for Surfaces

12.07.2018 | Event News

11th European Wood-based Panel Symposium 2018: Meeting point for the wood-based materials industry

03.07.2018 | Event News

 
Latest News

Leading experts in Diabetes, Metabolism and Biomedical Engineering discuss Precision Medicine

13.07.2018 | Event News

Research finds new molecular structures in boron-based nanoclusters

13.07.2018 | Materials Sciences

Algae Have Land Genes

13.07.2018 | Life Sciences

VideoLinks
Science & Research
Overview of more VideoLinks >>>