Genetic Aspects of Multiple Mieloma

Multiple myeloma (MM) is characterized by significant heterogeneity of clinical indicators, biological characteristics and effect on treatment. Data received during the study pointed to the hypothesis that this toxicity is caused by molecular characteristics of the tumor clone. Kariоtype at (MM) is complex of cause, including quantity (amount of chromosomes), and quality (structure of chromosomes) components. The translocations of immunoglobulins heavy chains play an important role in the pathogenesis of the disease in about half of the patients. An important feature of the karyotype of patients without translocations data is hyperploidy. Changes in the karyotype, which are repeated more often than others, include hyperploidy, loss of 13th chromosome and some specific translocations such as t(11; 14) (q13; q32); t(4; 14) (p16; q32); t(14; 16 ) (q23; q32). In the presented article the effect of known genetic anomalies on the pathogenesis of MM and the prognosis of the disease will be analyzed for choosing the optimal treatment strategy for the patient. With the help of karyotyping, quantitative chromosome changes can be more accurately determined. Limitation of the method of conventional cytogenetic analysis in MM is associated with low proliferative capacity of plasma cells, as well as a different degree of the bone marrow infiltration by these cells. With this method cytogenetic anomalies are detected in 40% of cases, and only 20-35% at the time of diagnosis. The frequency and number of changes in the karyotype at MM correlate with the stage of the disease and the response to treatment. Thus, in patients with I stage, cytogenetic anomalies are determined at 20%; at stage III, this index reaches 60%, while in the case of extramedular form of disease is more than 80%. From the clinical point of view, the translocation t(4; 14) has the greatest significance. The results of many studies indicate that patients with this translocation have a bad prognosis. Interestingly, some new specific therapeutic agents, such as proteasome inhibitors or immunomodulators are prescribed to these patients. It has already become known that only deletion of 13th chromosome is not a predictor of bad diagnosis. The most important for the forecast is the deletion of the 17th. This deletion occurs in 8-10% of patients with MM and is associated with extremely short survival, regardless of therapy. The molecular target of this deletion could be TR53, but there is not enough biological evidence in favor of this hypothesis, in addition, the mutations of this gene are observed only in patients. There are several scientific articles about an additional 1q chromosome (observed in a 1/3 of patients), which also indicates a bad prognosis. This pathology is a secondary event not specific to MM, acquired during the evolution of the disease. (Miel-ful)