Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Hodgkin Lymphoma - New Characteristics Discovered

08.10.2008
Researchers are still discovering new characteristics of Hodgkin lymphoma, a common form of cancer of the lymphatic system. The malignant cells are derived from white blood cells (B cells), but have lost a considerable part of the B cell-specific gene expression pattern.

Björn Lamprecht and Dr. Stephan Mathas (Max Delbrück Center for Molecular Medicine, MDC, Berlin-Buch and Charité - Universitätsmedizin Berlin, Germany) have now demonstrated the production of interleukin 21 (IL-21) in the tumor cells of Hodgkin lymphoma. IL-21 promotes the growth of cancer cells and helps them evade immune system detection (Blood*, Vol. 112. N0. 8, 2008, 3339-3347).

Until now IL-21 was thought to be produced only by T cells, another group of immune cells. Blocking IL-21 production could lead to the development of new therapy strategies for Hodgkin lymphoma in the future, according to the researchers in Professor Bernd Dörken's laboratory, who collaborated with researchers at the University Tor Vergata, Rome (Italy).

It was not until 1994, some 160 years after Hodgkin's lymphoma (HL) was first described by the British physician Thomas Hodgkin (1832), that - using molecular biological methods - scientists discovered that the disease originates from the white blood cells, the B cells. They noticed, however, that the malignant Hodgkin/Reed-Sternberg (HRS) cells of Hodgkin lymphoma (HL) exhibit a phenotype and characteristics that are considerably altered. Although HRS cells are derived from B cells, they have lost the expression of most of the B cell genes due to reprogramming.

The research hypothesis of the just-published paper was that the tumor cells, due to the loss of many B-cell specific genes, need alternative signaling pathways to maintain their malignant growth. As Dr. Mathas explained, "Reprogramming can provide the cells of Hodgkin ymphoma with this survival advantage." Hence, the researchers were searching for factors that normally do not originate from B cells. They found what they were looking for in the gene for the cytokine IL-21.

Different Functions of IL-21
It has only been a few years since IL-21 was discovered in T cells. The function of IL-21, however, varies greatly depending on the kind of cell. In some cell types IL-21 stimulates the body's protection program, which researchers call programmed cell death or apoptosis. Each cell contains this apoptosis program so that it will self-destruct when it is altered or defective. This prevents the defective cell from damaging the entire organism.

Thus, IL-21 stimulates the T cells of the immune system and, for instance, drives cells of the chronic-lymphatic leukemia of the B-cell type (B-CLL) to apoptosis. By contrast, in T-cell leukemias, IL-21 does just the opposite and stimulates malignant growth. For the first time, the researchers from Berlin and Rome were able to show that IL-21 is produced by lymphatic cells originally derived from B cells. IL-21 activates a specific signaling pathway (STAT3), thus up-regulating the expression of a group of specific genes in HRS cells which support the unchecked growth and survival of HRS cells.

IL-21 also activates a chemoattractant for cells which suppress the immune system

On top of that, according to further findings of the researchers, IL-21 activates a protein (MIP-3 alpha) in the HRS cells that attracts a group of T cells to the tumor which suppress the immune system. In the healthy organism, these regulatory T cells keep the immune system in check and prevent excessive immune responses.

In proximity to the HRS cells there are a large number of these regulatory T cells. Attracted by MIP-3-alpha, they can suppress an effective immune defense of the body against the HRS cells. The production of such chemoattractants could, according to the researchers, also be a cause for why Hodgkin lymphoma contains so few tumor cells. They comprise merely 0.1 to one percent of the tissue.

Animal experiments have shown that in immunological diseases like rheumatoid arthritis and lupus erythematosus, a disease accompanied by symptoms such as skin changes and inflammation of blood vessels and joints, these symptoms can be significantly improved if IL-21 is inhibited. "If we could block IL-21 or also MIP-3 alpha in human tumor cells," Dr. Mathas added, "this might be a new therapeutic approach for Hodgkin lymphoma." The present cure rate for the disease - also in its advanced stages - is 80 to 90 percent, particular when chemotherapy is used. However, these therapy regimens might have severe side ffects including the risk of therapy-induced secondary malignancies.

Only recently Dr. Mathas and Dr. Martin Janz were distinguished for their research on Hodgkin ymphoma with the Curt Meyer Memorial Prize of the Berlin Cancer Society.

*Aberrant expression of the Th2 cytokine IL-21 in Hodgkin lymphoma cells regulates STAT3 signaling and attracts Treg cells via regulation of MIP-3 alpha

Björn Lamprecht1,2, Stephan Kreher1,2, Ioannis Anagnostopoulos4, Korinna Jöhrens4, Giovanni Monteleone3, Franziska Jundt1,2, Harald Stein4, Martin Janz1,2, Bernd Dörken1,2 and Stephan Mathas1,2

1Max-Delbrück-Center for Molecular Medicine, Robert-Rössle-Str. 10, 13125 Berlin;2Hematology, Oncology and Tumorimmunology, Charité, Medical University Berlin, CVK, Augustenburger Platz 1, 13353 Berlin; 3Dipartimento di Medicina Interna e Centro di Eccellenza per lo Studio delle Malattie Complesse e Multifattoriali, Università Tor Vergata, Rome, Italy; 4Institute for Pathology, Charité, Medical University Berlin, CBF, Hindenburgdamm 30, 12200 Berlin, Germany; prepublished online August 6, 2008; DOI 10.1182/blood-2008-01-134783

Barbara Bachtler
Press and Public Affairs
Max Delbrück Center for Molecular Medicine (MDC) Berlin-Buch
Robert-Rössle-Straße 10; 13125 Berlin; Germany
Phone: +49 (0) 30 94 06 - 38 96
Fax: +49 (0) 30 94 06 - 38 33
e-mail: presse@mdc-berlin.de

Barbara Bachtler | Max-Delbrück-Centrum
Further information:
http://www.mdc-berlin.de/
http://www.mdc-berlin.de/en/news/2005/index.html
http://www.lymphome.de/en/

More articles from Life Sciences:

nachricht Researchers identify potentially druggable mutant p53 proteins that promote cancer growth
09.12.2016 | Cold Spring Harbor Laboratory

nachricht Plant-based substance boosts eyelash growth
09.12.2016 | Fraunhofer-Institut für Angewandte Polymerforschung IAP

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Electron highway inside crystal

Physicists of the University of Würzburg have made an astonishing discovery in a specific type of topological insulators. The effect is due to the structure of the materials used. The researchers have now published their work in the journal Science.

Topological insulators are currently the hot topic in physics according to the newspaper Neue Zürcher Zeitung. Only a few weeks ago, their importance was...

Im Focus: Significantly more productivity in USP lasers

In recent years, lasers with ultrashort pulses (USP) down to the femtosecond range have become established on an industrial scale. They could advance some applications with the much-lauded “cold ablation” – if that meant they would then achieve more throughput. A new generation of process engineering that will address this issue in particular will be discussed at the “4th UKP Workshop – Ultrafast Laser Technology” in April 2017.

Even back in the 1990s, scientists were comparing materials processing with nanosecond, picosecond and femtosesecond pulses. The result was surprising:...

Im Focus: Shape matters when light meets atom

Mapping the interaction of a single atom with a single photon may inform design of quantum devices

Have you ever wondered how you see the world? Vision is about photons of light, which are packets of energy, interacting with the atoms or molecules in what...

Im Focus: Novel silicon etching technique crafts 3-D gradient refractive index micro-optics

A multi-institutional research collaboration has created a novel approach for fabricating three-dimensional micro-optics through the shape-defined formation of porous silicon (PSi), with broad impacts in integrated optoelectronics, imaging, and photovoltaics.

Working with colleagues at Stanford and The Dow Chemical Company, researchers at the University of Illinois at Urbana-Champaign fabricated 3-D birefringent...

Im Focus: Quantum Particles Form Droplets

In experiments with magnetic atoms conducted at extremely low temperatures, scientists have demonstrated a unique phase of matter: The atoms form a new type of quantum liquid or quantum droplet state. These so called quantum droplets may preserve their form in absence of external confinement because of quantum effects. The joint team of experimental physicists from Innsbruck and theoretical physicists from Hannover report on their findings in the journal Physical Review X.

“Our Quantum droplets are in the gas phase but they still drop like a rock,” explains experimental physicist Francesca Ferlaino when talking about the...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

ICTM Conference 2017: Production technology for turbomachine manufacturing of the future

16.11.2016 | Event News

Innovation Day Laser Technology – Laser Additive Manufacturing

01.11.2016 | Event News

#IC2S2: When Social Science meets Computer Science - GESIS will host the IC2S2 conference 2017

14.10.2016 | Event News

 
Latest News

Researchers identify potentially druggable mutant p53 proteins that promote cancer growth

09.12.2016 | Life Sciences

Scientists produce a new roadmap for guiding development & conservation in the Amazon

09.12.2016 | Ecology, The Environment and Conservation

Satellites, airport visibility readings shed light on troops' exposure to air pollution

09.12.2016 | Health and Medicine

VideoLinks
B2B-VideoLinks
More VideoLinks >>>