Blood cancer cells initiate signalling cascade

August 13, 2012
Blood cancer cells initiate signalling cascade
In patients with Chronic Lymphocytic Leukaemia, two receptors dock at the outside of white blood cells (top, in blue) and use receptor components at the inside of the cell (bottom) to trigger a signalling cascade. This in turn is an important step of the conversion into an uncontrolled dividing cancer cell. Image: Dühren-von Minden

Researchers in the group of Prof. Dr. Hassan Jumaa, Centre for Biological Signalling Studies (BIOSS) of the University of Freiburg, Department for Molecular Immunology, have identified a new mechanism that causes immune cells to convert into malignant cancer cells. In Chronic Lymphocytic Leukaemia (CLL), one of the most common types of blood cancer in the Western world, cells themselves carry the key for the pathogenic transformation, the scientists report in the journal Nature. Understanding these underlying mechanisms could facilitate new therapies with reduced side effects.

In healthy humans, a subgroup of , so-called B-lymphocytes, are responsible for producing antibodies that fight infections. Special of B-lymphocytes detect pathogenic agents via the key-lock principle and consequently start producing antibodies. In patients with CLL, however, abnormal forms of these receptors lead to uncontrolled reproduction of malignant B-lymphocytes. As a result, healthy cells of the immune system get repressed.

“Up to now, it was assumed that agents produced in the bodies of patients dock at the receptor and thereby activate CLL lymphocytes”, Jumaa says. “In our study we could show that specific components of the receptors are responsible for the development of CLL.” In B-lymphocytes of CLL patients, receptor components FR2 and HCDR3 are formed in such a manner that they represent key and lock of the receptor. “Hereby, neighbouring receptors of the same cells activate each other and trigger a signalling cascade, which finally causes uncontrolled division of cancer cells.”

Currently, approaches like chemotherapy that suppress symptoms in a relatively unspecific manner are applied in CLL treatment. “Based on decoding the molecular basics of CLL, we now strive to translate this knowledge to make it useful for patients”, Marcus Dühren-von Minden says, another author of the study. “It is conceivable to administer numerous copies of the key FR2 to patients, which then dock to the receptors and prevent neighbouring receptors to bind at each other. This stops the consequential signalling cascade.” Through this mechanism, the course of the disease could be precluded much earlier than before, and with less side effects.

Explore further: Agent selectively targets malignant B cells in chronic leukemia, study shows

More information: M Dühren-von Minden, R Übelhart, D Schneider, T Wossning, MP Bach, M Buchner, D Hofmann, E Surova, M Follo, F Köhler, H Wardemann, K Zirlik, H Veelken, H Jumaa. Chronic lymphocytic leukemia is driven by antigen-independent cell autonomous signaling. Nature, electronic publication ahead of print. DOI 10.1038/nature11309

Related Stories

Agent selectively targets malignant B cells in chronic leukemia, study shows

May 3, 2011
A new experimental drug selectively kills the cancerous cells that cause chronic lymphocytic leukemia, according to a new study by researchers at the Ohio State University Comprehensive Cancer Center – Arthur G. James ...

New biomarker may predict prognosis for patients with chronic lymphocytic leukemia

April 24, 2012
Researchers at the University of California-San Diego School of Medicine have shown that G protein-coupled receptor expression may predict the prognosis of patients with chronic lymphocytic leukemia. Their findings may identify ...

Stem cells central to pathogenesis of mature lymphoid tumors

August 15, 2011
New research suggests that blood stem cells can be involved in the generation of leukemia, even when the leukemia is caused by the abnormal proliferation of mature cells. The study, published by Cell Press in the August 16th ...

Decoding chronic lymphocytic leukemia

June 13, 2011
A paper published online on June 13 in the Journal of Experimental Medicine identifies new gene mutations in patients with chronic lymphocytic leukemia (CLL) -- a disease often associated with lack of response to chemotherapy ...

Researchers find new hope for treatment of chronic leukemia

August 17, 2011
While testing a new drug designed to treat chronic leukemia, researchers at Cleveland Clinic discovered new markers that could identify which patients would receive maximum benefit from the treatment.

Recommended for you

Study prompts new ideas on cancers' origins

December 16, 2017
Rapidly dividing, yet aberrant stem cells are a major source of cancer. But a new study suggests that mature cells also play a key role in initiating cancer—a finding that could upend the way scientists think about the ...

What does hair loss have to teach us about cancer metastasis?

December 15, 2017
Understanding how cancer cells are able to metastasize—migrate from the primary tumor to distant sites in the body—and developing therapies to inhibit this process are the focus of many laboratories around the country. ...

Cancer immunotherapy may work better in patients with specific genes

December 15, 2017
Cancer cells arise when DNA is mutated, and these cells should be recognized as "foreign" by the immune system. However, cancer cells have found ways to evade detection by the immune system.

Scientists pinpoint gene to blame for poorer survival rate in early-onset breast cancer patients

December 15, 2017
A new study led by scientists at the University of Southampton has found that inherited variation in a particular gene may be to blame for the lower survival rate of patients diagnosed with early-onset breast cancer.

Scientists unlock structure of mTOR, a key cancer cell signaling protein

December 14, 2017
Researchers in the Sloan Kettering Institute have solved the structure of an important signaling molecule in cancer cells. They used a new technology called cryo-EM to visualize the structure in three dimensions. The detailed ...

'Bet hedging' explains the efficacy of many combination cancer therapies

December 14, 2017
The efficacy of many FDA-approved cancer drug combinations is not due to synergistic interactions between drugs, but rather to a form of "bet hedging," according to a new study published by Harvard Medical School researchers ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.