MOLECULAR AND GENETIC RISK FACTORS FOR THE DEVELOPMENT OF THROMBOTIC AND HEMORRHAGIC COMPLICATIONS IN ESENTIAL THROMBOCYTHEMIA

Аннотация

Essential thrombocythemia (ET) is a pathology of clonal hematopoietic stem cells that leads to increased platelet production. Pathogenetically, ET is a bone marrow disease in which megakaryocyte proliferation leads to persistent hyperthrombocytosis with the risk of vascular thrombosis and thromboembolism. The etiology of the disease has not yet been established. The leading hypothesis is the polyethological nature of the disease occurrence, where the predisposition to the disease is realized under the influence of external factors that damage the genome of a normal cell and lead to its malignant transformation Molecular genetic analysis of JAK2 V617F, JAK2 exon12, MPL W515K/L, and CALR mutations plays an exceptional role in the diagnosis of classic Ph-negative MPN. However, genes that control signal transmission within the cell, chromatin remodeling, DNA methylation, oncogenes, and tumor suppressors are involved in the development of these diseases. Current knowledge suggests that the JAK2 V617F mutation may not be the first event in the complex pathogenesis of myeloproliferative diseases (MPD). This review describes the current understanding of molecular genetic disorders that are risk factors and affect the development of thrombotic and hemorrhagic complications in ET.