Press Release: New hope for patients with cancer of the lymphatic tissue (29.9.2016)
Prague, Vestec, September 26, 2016 – In the Czech Republic, lymphomas develop in up to two and a half thousand people every year. The overall incidence in the Czech Republic is estimated to be around twenty-five thousand patients. Thanks to its collaboration with BIOCEV, the First Faculty of Medicine of Charles University (First FM CU) and the First Department of Internal Medicine at General University Hospital (First DIM GUH), it was possible to identify new therapeutic targets that serve as a specific therapy against tumours of the lymphatic system. The success of the Czech team of scientists and physicians was published on 23 September 2016, in the scientific journal Blood Cancer.
Lymphomas are cancers arising from cells of the lymph nodes, otherwise known as lymphocytes. They are divided into two categories: Hodgkin’s lymphoma and non-Hodgkin’s lymphoma (NHL). Non-Hodgkin’s lymphomas, together with chronic lymphocytic leukaemia (CLL,) are the most common cancers based on white blood cells. The research work of Czech scientists studies the aggressive type of NHL called mantle cell lymphoma (MCL), which is among the third most common type of NHL and typically affects more men than women (at a ratio of 2-3:1). MCL is characterized not only by extensive presence of swollen lymph nodes, but also the presence of lymphoma cells in the patient’s bone marrow (marrow infiltration) and blood (leukaemization). Despite therapeutic advances, MCL is still considered an incurable disease even when currently available drugs are used.
Prof. Tomas Stopka, one of the authors of the publication, clinical haematologist and the head of StopkaLab in the BIOCEV science centre, comments on that as follows: “Drug development faces a fundamental problem, which is our lack of understanding of tumour-specific mechanisms. This means that we need to find out what processes in the human body can be slowed down or eliminated by treatment so as to limit the development of lymphoma while keeping healthy tissues unaffected.” Prof. Stopka also adds: “Human cells have the ability to produce about thirty thousand different proteins in various tissues. We managed to identify and describe six of these proteins which are highly active in specific subtypes of lymphoma. It is exactly this research on such phenomena that leads to the development of drugs that can specifically remove a particular subtype of lymphoma”.
How was this achieved? Researchers compared the production of molecules consisting of cells of two major lymphoma subtypes, MCL and CLL, to normal healthy lymphocytes. They found that CLL and MCL share 216 substances that are not produced to such an extent by normal healthy cells. By contrast, only 6 substances are preferably produced in MCL or CLL: 3 are significant for MCL and 3 for CLL. Among the substances that play a role in MCL and which were further studied, the researchers discovered a protein known as MARCKS. This is a signalling protein that is a substrate of a cascade of enzymes called protein kinase C. MARCKS is not only overexpressed in MCL, but also accumulates in the cytoplasm of MCL tumour cells and is maintained in an active (phosphorylated) state. The scientific work also describes why MARCKS is overexpressed just in MCL and shows the importance of small non-coding RNAs, known as microRNAs, which are behind the development of lymphomas.
Doc. Pavel Klener, who deals with basic research on the pathogenesis of MCL and also is among the most significant clinical hematologists at the Clinic of Prof. Trneny, focusing on patients with lymphoma, remarks: “Collaboration between teams from the First FM CU is also important because it interconnects teams with diverse expertise, which currently leads to the development of other studies that expand the range of our activities to other hematologic diseases. By linking the projects of the GUH, the First FM CU and BIOCEV with the Czech Centre for Phenogenomics, for example, it will be possible to study the development of lymphomas isolated from patients within an animal model and use those results to test new treatment options.”
More information about the publication: J. Vargova, K. Vargova, N. Dusilkova, V. Kulvait, V. Pospisil, J. Zavadil., M. Trneny, P. Klener and T. Stopka. Differential expression, localization and activities of MARCKS between mantle cell lymphoma and chronic lymphocytic leukaemia. Blood Cancer Journal (2016) 6, e475; doi: 10.1038/bcj.2016.80; published online on 23 September 2016, reference: http://www.nature.com/doifinder/10.1038/bcj.2016.80
The BIOCEV Centre (http://www.biocev.eu) is a joint project of two faculties of Charles University (The First Faculty of Medicine and the Faculty of Science) and six institutes from the Academy of Sciences of the Czech Republic. Currently, this biotechnology and biomedical centre in Vestec employs about 400 scientific and technical workers. Almost one-third of them come from abroad. Their common goal is to conduct detailed studies of organisms at the molecular level, which will inspire applied research and the development of new treatments.
One of the 53 laboratories based in the BIOCEV Centre is headed by Prof. Tomas Stopka and is called StopkaLab (http://stopka-lab.lf1.cuni.cz). It brings together experts from different specializations: biologists, mathematicians, biochemists and physicians. It conducts basic research in the field of haematological malignancies, focusing on genetics and epigenetics. The above-described success of the research project achieved by workers from BIOCEV and the First DIM GUH was made possible through funding agencies (GACR and AZV) and Charles University within the UNCE project.
The Czech Centre for Phenogenomics (CCP) is one of six research infrastructures at BIOCEV and also the largest institution of its kind in Central Europe. The CCP also includes a transgenic laboratory producing specialized genetically modified mouse models that serve as tools for studying the function of genes for both the Czech and international scientific communities. Together with foreign colleagues, the team of Doc. Radislav Sedlacek, head of the CCP, are participating in the international program entitled “Encyclopedia of functions of mammalian genes”, focusing on a primary description of functions of all the genes within the next ten years. The results of their research may positively influence the treatment of serious diseases.
The First Department of Internal Medicine at General University Hospital in Prague and the First Faculty of Medicine of Charles University are among the top centres engaged in the treatment of haematological diseases. It is one of seven centres providing haematological intensive care in the Czech Republic and a leading medical centre in the diagnosis and treatment of lymphomas, chronic lymphocytic leukaemia, multiple myeloma and myelodysplastic syndrome. It also focuses on other diseases such as chronic myelogenous leukaemia, acute leukaemia in older patients, anaemia and various types of cytopenias. With its program of autologous transplantation of hematopoietic cells, it is among the centres that performs the largest number of transplantations in the country. At the clinic, there is a national registry of patients with lymphoma and myelodysplastic syndrome as well as a national registry of completed transplantations of hematopoietic cells.