Molecular Genetic Abnormalities in the Pathogenesis of Hematologic Malignancies and Corresponding Changes in Cell Signaling Systems

Abstract

Hematological disorders include a wide spectrum of malignancies of hematopoietic and lymphoid tissues. The genetic changes underlying the pathogenesis of the diseases are specific for each disease. High incidence of chromosomal aberrations (deletion, translocation, insertion) is one of the principal characteristics of oncohematological diseases. In addition, mutations in individual genes or blocking of normal regulation of gene functioning in relation to epigenetic events can occur. Progression of oncohematological diseases could be a result of accumulation of different genetic abnormalities. Modern classification of malignancies of hematopoietic and lymphoid tissues is based on the analysis of clinical data, morphological and functional characteristics of tumor cells and identification of specific cytogenetic and molecular-genetic changes. A large number of genetic abnormalities specific for certain types of hematological malignancies has been discovered to date. It allows to optimize the treatment strategy, as well as to design, test and introduce to the clinical practice a number of targeted drugs (inhibitors of chimeric proteins formed as a result of trans-locations and triggering the malignant cell transformation). Drugs based on monoclonal antibodies (Rituximab, Alemtuzumab, etc.) or low molecular weight compounds (Imatinib, Bortezomib, Carfilzomib) form this group of medications. The knowledge about not only specific gene abnormalities but also about the corresponding changes in cell efferent signaling pathways could be of great interest for the development of new targeted molecules or the repurposing of known chemotherapeutic agents. The present review compares genetic aberrations in diseases listed in the 2008 WHO classification (amended in 2016) of hematopoietic and lymphoid tissue malignancies and main changes in cell signaling pathways associated with malignant transformation of hematopoietic cells.