Featured Research

from universities, journals, and other organizations

Leukemia cells are 'bad to the bone', research finds

Date:
January 27, 2012
Source:
University of Rochester Medical Center
Summary:
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.

Graduate student Ben Frisch and Laura Calvi, M.D.
Credit: Image courtesy of University of Rochester Medical Center

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.

Related Articles


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.


Story Source:

The above story is based on materials provided by University of Rochester Medical Center. Note: Materials may be edited for content and length.


Journal References:

  1. B. J. Frisch, J. M. Ashton, L. Xing, M. W. Becker, C. T. Jordan, L. M. Calvi. Functional inhibition of osteoblastic cells in an in vivo mouse model of myeloid leukemia. Blood, 2011; 119 (2): 540 DOI: 10.1182/blood-2011-04-348151
  2. S. W. Lane. Bad to the bone. Blood, 2012; 119 (2): 323 DOI: 10.1182/blood-2011-10-383901

Cite This Page:

University of Rochester Medical Center. "Leukemia cells are 'bad to the bone', research finds." ScienceDaily. ScienceDaily, 27 January 2012. <www.sciencedaily.com/releases/2012/01/120126161129.htm>.
University of Rochester Medical Center. (2012, January 27). Leukemia cells are 'bad to the bone', research finds. ScienceDaily. Retrieved April 2, 2015 from www.sciencedaily.com/releases/2012/01/120126161129.htm
University of Rochester Medical Center. "Leukemia cells are 'bad to the bone', research finds." ScienceDaily. www.sciencedaily.com/releases/2012/01/120126161129.htm (accessed April 2, 2015).

Share This


More From ScienceDaily



More Health & Medicine News

Thursday, April 2, 2015

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Wound-Healing Laser Soon to Be a Reality Israeli Scientist

Wound-Healing Laser Soon to Be a Reality Israeli Scientist

Reuters - Innovations Video Online (Apr. 1, 2015) Israeli scientists says laser bonding of tissue allows much faster healing and less scarring. Amy Pollock has more. Video provided by Reuters
Powered by NewsLook.com
Liberia Sees Resurgence of Drug Trafficking as Ebola Wanes

Liberia Sees Resurgence of Drug Trafficking as Ebola Wanes

AFP (Apr. 1, 2015) The governments of Liberia and Sierra Leone have been busy fighting the menace created by the deadly Ebola virus, but illicit drug lords have taken advantage of the situation to advance the drug trade. Duration: 01:12 Video provided by AFP
Powered by NewsLook.com
Stigma Stalks India's Leprosy Sufferers as Disease Returns

Stigma Stalks India's Leprosy Sufferers as Disease Returns

AFP (Apr. 1, 2015) The Indian government declared victory over leprosy in 2005, but the disease is making a comeback in some parts of the country, with more than a hundred thousand lepers still living in colonies, shunned from society. Duration: 02:41 Video provided by AFP
Powered by NewsLook.com
7-Year-Old Girl Gets 3-D Printed 'robohand'

7-Year-Old Girl Gets 3-D Printed 'robohand'

AP (Mar. 31, 2015) Although she never had much interest in prosthetic limbs before, Faith Lennox couldn&apos;t wait to slip on her new robohand. The 7-year-old, who lost part of her left arm when she was a baby, grabbed it as soon as it came off a 3-D printer. (March 31) Video provided by AP
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:

Breaking News:

Strange & Offbeat Stories


Health & Medicine

Mind & Brain

Living & Well

In Other News

... from NewsDaily.com

Science News

Health News

Environment News

Technology News



Save/Print:
Share:

Free Subscriptions


Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

Get Social & Mobile


Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

Have Feedback?


Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
Mobile: iPhone Android Web
Follow: Facebook Twitter Google+
Subscribe: RSS Feeds Email Newsletters
Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins