Projects & Grants
|Molecular characterization of newly identified protein markers in residual multiple myeloma resistant to antitumor therapy
|doc. RNDr. Michal Šimíček, PhD.
|1/2019 - 12/2020
|Specifický VŠ výzkum
|Multiple myeloma (MM) is the second most common cancer of the immune system cells affecting the elderly. This disease is caused by tumor transformation of the plasma cells in the bone marrow and their subsequent proliferation and aberrant production of a monoclonal protein (so-called paraprotein). As a result, the malignant cells directly cause severe bone damage and indirectly cause immunodeficiency and impair function of important organs via production of paraprotein. The main challenge in the treatment of MM is the genetic heterogeneity of malignant cells and the resistance of some clones to current tumor therapies. Upon treatment, some clones can survive at the stage of minimal residual disease (MRD) and subsequently relapse. For the complete elimination of these residual clones, it is crucial to determine which proteins and molecular mechanisms cause resistance and these target for further treatment. For many years, The Blood Cancer Research Group at the Hematooncology Clinic at the FNO under the leadership of prof. Roman Hájek has been very successful in MM research Recently, a unique, extensive study has been carried out to detect pathogenic mutations in residual clones of MM isolated from the bone marrow at the stage of MRD by using the New generation sequencing (NGS) and subsequent bioinformatics analysis. The study revealed the mutational profile of aberrant clones and lead to the identification of several new candidate protein markers that can play a crucial role in resistance to therapy. The aim of this project proposal is to use our results obtained so far and focus on functional characterization of candidate proteins using molecular biology, cell biology, and biochemical approaches. The result of this project will be a better understanding of the functional significance of genetic changes in MM and the identification of new therapeutic targets.