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.
Scott LaFee | EurekAlert!
A promising target for kidney fibrosis
21.04.2017 | Brigham and Women's Hospital
Stem cell transplants: activating signal paths may protect from graft-versus-host disease
20.04.2017 | Technische Universität München
More and more automobile companies are focusing on body parts made of carbon fiber reinforced plastics (CFRP). However, manufacturing and repair costs must be further reduced in order to make CFRP more economical in use. Together with the Volkswagen AG and five other partners in the project HolQueSt 3D, the Laser Zentrum Hannover e.V. (LZH) has developed laser processes for the automatic trimming, drilling and repair of three-dimensional components.
Automated manufacturing processes are the basis for ultimately establishing the series production of CFRP components. In the project HolQueSt 3D, the LZH has...
Reflecting the structure of composites found in nature and the ancient world, researchers at the University of Illinois at Urbana-Champaign have synthesized thin carbon nanotube (CNT) textiles that exhibit both high electrical conductivity and a level of toughness that is about fifty times higher than copper films, currently used in electronics.
"The structural robustness of thin metal films has significant importance for the reliable operation of smart skin and flexible electronics including...
The nearby, giant radio galaxy M87 hosts a supermassive black hole (BH) and is well-known for its bright jet dominating the spectrum over ten orders of magnitude in frequency. Due to its proximity, jet prominence, and the large black hole mass, M87 is the best laboratory for investigating the formation, acceleration, and collimation of relativistic jets. A research team led by Silke Britzen from the Max Planck Institute for Radio Astronomy in Bonn, Germany, has found strong indication for turbulent processes connecting the accretion disk and the jet of that galaxy providing insights into the longstanding problem of the origin of astrophysical jets.
Supermassive black holes form some of the most enigmatic phenomena in astrophysics. Their enormous energy output is supposed to be generated by the...
The probability to find a certain number of photons inside a laser pulse usually corresponds to a classical distribution of independent events, the so-called...
Microprocessors based on atomically thin materials hold the promise of the evolution of traditional processors as well as new applications in the field of flexible electronics. Now, a TU Wien research team led by Thomas Müller has made a breakthrough in this field as part of an ongoing research project.
Two-dimensional materials, or 2D materials for short, are extremely versatile, although – or often more precisely because – they are made up of just one or a...
20.04.2017 | Event News
18.04.2017 | Event News
03.04.2017 | Event News
24.04.2017 | Physics and Astronomy
24.04.2017 | Materials Sciences
24.04.2017 | Life Sciences