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Scientists identified signaling pathway in lymphoma

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Posted April 13, 2015

Researchers from the University of Zurich have recently conducted a study to demonstrate that the central signaling pathway in lymphoma, a malignant type of blood cancer, can be blocked successfully using compounds that are already in clinical development. This means that in the future the diagnosis, prognosis and treatment of this disease can be much easier and have better results.

Micrograph of a diffuse large B cell lymphoma. It is an aggressive tumour which can arise in virtually any part of the body and is always fatal if left untreated. Image credit: Nephron via Wikimedia, CC BY-SA 3.0

Micrograph of a diffuse large B cell lymphoma. It is an aggressive tumour which can arise in virtually any part of the body and is always fatal if left untreated. Image credit: Nephron via Wikimedia, CC BY-SA 3.0

The researchers have identified a key signaling pathway in B-cell lymphoma. Even though, this disease is always fatal if left untreated, the cure rate after chemotherapy combined with antibodies approaches 60 to 70 percent. However, as the biology of this type of lymphoma remains poorly understood, prognosis for the patients is usually a hard task. But now this new study finds that newly identified signaling pathway can be attacked efficiently using substances that are already in clinical development for other diseases.

To start the research scientists created a hypothesis that not only genetic, but also epigenetic changes might play a crucial role in the development of lymphoma. They analyzed an epigenetic change, which controls the activity of many human genes across the genome, called methylation of DNA. When altered, it is a common feature of a wide variety of tumor types. That is why scientists were thinking that lymphoma cells might also use this regulatory mechanism to their advantage.

The research proved hypothesis to be correct – 70 patient samples revealed eight regions on the DNA, so-called gene loci, that were all abnormally hyper methylated and turned out to be important for the cells’ survival. Moreover, scientists made another discovery that is described as ‘astonishing’ by the University of Zurich. In several large patient cohorts, the epigenetic silencing of this gene locus proved to be an extremely significant, negative prognostic factor for the long-term survival of diffuse large B-cell lymphoma patients.

The newly identified gene locus contains the genetic information for an enzyme, a phosphatase, which regulates an important signaling pathway in the lymphoma cells and is evidently essential for the tumor cells to survive. It makes it an important new target for future treatments of the disease. The researchers were now able to demonstrate that these inhibitors, which are already under clinical development, are also effective against lymphoma cells in cell cultures and in an animal model. In short, experiments with mice showed that the compound slows down the growth of lymphomas – lymphomas in mice treated with the compound grew considerably more slowly than those in untreated mice.

This is a rather rare example when scientific discoveries have a clear path into clinical applications. Further research is going to be needed, but even now it is evident that results of this study could be important for the diagnosis and prognosis of the lymphoma, as well as therapeutic decisions in the near future.

Source: UZH

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