The discovery of the molecular mechanism underlying the development of lymphoma

07.11.2016

Researchers from National Institute of Chemistry and the Centre of Excellence EN- FIST, Ljubljana, Slovenia in collaboration with researchers from the University of Tübingen, Germany, discovered the molecular mechanism of activation of the signaling pathways necessary for the survival of cancer cells occuring in some types of lymphoma .

Researchers from National Institute of Chemistry and the Centre of Excellence EN- FIST, Ljubljana, Slovenia in collaboration with researchers from the University of Tübingen, Germany, discovered the molecular mechanism of activation of the signaling pathways necessary for the survival of cancer cells occuring in some types of lymphoma .



Four years ago, researchers from the US observed that certain types of lymphoma (ABC DLBCLs), a cancer of the white blood cells, harbor frequent mutations of the protein involved in sensing bacterial and viral infections. This protein, called MyD88, integrates signals from several TLR receptors, discovered by Bruce Beutler and Jules Hoffman, Nobel Prize winners for medicine in 2011. Researchers from the National Institute of Chemistry have discovered that afore mentioned mutation causes the aggregation of mutated proteins enabling the activation of signaling pathways that prevents the death of cancer cells. It was shown that during the development of cancer, mutations that increased the activation and thus the survival of cancer cells were selected. Furthermore, researchers from Slovenia and Germany discovered that mutation in only one allelic copy of the MyD88 gene is sufficient for the activation, since mutated proteins can aggregate with the MyD88 present in normal cells. It was also shown that cancer cells were killed by the addition of a peptide that prevents dimerization of MyD88. The research combined molecular and cellular immunology approaches with molecular simulations.
Authors of the publication are Monika Avbelj, Ota Fekonja, Mojca Benčina, Matej Repič, Janez Mavri, Gabriela Panter and Roman Jerala from the National Institute of Chemistry and the Centre of Excellence EN- FIST and 5 researchers from the University of Tübingen. The article appeared in the early online edition of the journal Blood, the leading journal in the field of hematology. Researchers emphasize that the activity of the peptide used in the study is currently too weak for therapeutic usage; however the results open the path for the development of more effective therapeutics.