Skip Ribbon Commands
Skip to main content
Translate
Translate
menu iconMenu
search iconSearch

The Mouse That ROR’ed

ROR1 oncogene combines with another to accelerate, worsen blood cancer

January 02, 2014  |  

Researchers at the University of California, San Diego School of Medicine report that an oncogene dubbed ROR1, found on chronic lymphocytic leukemia (CLL) B cells but not normal adult tissues, acts as an accelerant when combined with another oncogene, resulting in a faster-developing, more aggressive form of CLL in mice.

The findings, published in the Dec. 30, 2013 Online Early Edition of PNAS, suggest ROR1 could be an important therapeutic target for patients with CLL, the most common form of blood cancer. Prevalence of CLL in the United States is high: 1 in 20 people over the age of 40 could  have apparently pre-cancerous CLL-like cells in their blood. These people may develop actual CLL at a rate of about 1 percent per year. More than 15,000 new cases of CLL are diagnosed each year in the United States. Roughly 4,400 patients with CLL die annually.

The work by principal investigator Thomas Kipps, MD, PhD, Evelyn and Edwin Tasch Chair in Cancer Research, and colleagues continues a series of discoveries about ROR1. Previously, for example, they found an association between ROR1 and the epithelial-mesenchymal transition – the process that occurs during embryogenesis when cells migrate and then grow into new organs during early development. CLL cells exploit ROR1 to spread disease. Called metastasis, it is responsible for 90 percent of cancer-related deaths.

In the PNAS paper, Kipps and colleagues created transgenic mice that expressed human ROR1, then observed that these mice produced B cells (a kind of white blood cell) that were abnormal and resembled human CLL cells while non-transgenic littermates did not.

Next they crossed the ROR1 mice with another transgenic mouse-type that produces an oncogene called TCL1. Oncogenes are genes that can lead to cancer development if over-expressed or mutated. The progeny of these cross-bred mice possessed both oncogenes – ROR1 and TCL1 – and consequently displayed an even greater proclivity toward developing aggressive, fast-acting CLL.

When researchers treated the mice with an anti-ROR1 monoclonal antibody that reduces levels of ROR1, the CLL cells were impaired and more vulnerable to treatment and destruction.  Based on these findings, Kipps said investigators at UC San Diego Moores Cancer Center are planning clinical trials in 2014 using a humanized monoclonal antibody that has the same type of activity against human leukemia or cancer cells that express ROR1.

Co-authors are George F. Widhopf II, Bing Cui, Emanuela M. Ghia and Liguang Chen, Department of Medicine, UCSD; Karen Messer, Department of Biostatistics/Bioinformatics, UCSD; Zhouxin Shen and Steven P. Briggs, Cell & Developmental Biology, UCSD; and Carlo M. Croce, Ohio State University School of Medicine.

Funding support came, in part, from the National Institutes of Health grants PO1-CA081534 and R37-CA049870, California Institute for Regenerative Medicine (DR1-01430) and the UC San Diego Foundation Blood Cancer Research Fund.

Disclosure: Thomas Kipps is a member of the Scientific Advisory Boards of Celgene Corporation and Igenica Inc, which have a financial interest in the reported research.

 


Browse

Related Specialties

Leukemia and Lymphoma



Media Contact

Scott LaFee
619-543-6163
slafee@ucsd.edu

Related News

5/1/2015
Researchers at UC San Diego School of Medicine conducted the first population-based study that characterizes the association and temporal relationship between gastrointestinal stromal tumors (GIST) an ...
5/1/2015
In proof-of-concept experiments, researchers at University of California, San Diego School of Medicine demonstrate the ability to tune medically relevant cell behaviors by manipulating a key hub in ce ...
4/29/2015
Researchers at University of California San Diego School of Medicine report pancreatic cancer rates are highest in countries with the least amount of sunlight. Low sunlight levels were due to a combin ...
11/7/2014
Hematopoietic stem cells (HSCs) give rise to all blood and immune cells throughout the life of vertebrate organisms, from zebrafish to humans. But details of their genesis remain elusive, hindering ef ...
9/16/2014
Researchers at the University of California, San Diego School of Medicine have launched a phase 1 human clinical trial to assess the safety and efficacy of a new monoclonal antibody for patients with ...
2/3/2014
Researchers at the University of California, San Diego School of Medicine have identified a protein critical to hematopoietic stem cell function and blood formation. The finding has potential as a new ...
12/13/2013
Researcher Thomas J. Kipps, MD, PhD, professor of medicine and deputy director of research operations at UC San Diego Moores Cancer Center, is principal investigator for one of six “Disease Team” awar ...
10/14/2013
The Leukemia & Lymphoma Society has awarded Thomas J. Kipps, MD, PhD, Distinguished Professor of Medicine at the University of California, San Diego School of Medicine, with a 5-year, $6.25 million Sp ...


Share This Article



Follow Us