Loss of Heterozygosity in the Circulating Tumor DNA and CD138+ Bone Marrow Cells in Multiple Myeloma.

Multiple myeloma (MM) is characterized by heterogeneity of tumor cells. The study of tumor cells from blood, bone marrow, plasmacytoma, etc., allows us to identify similarities and differences in tumor lesions of various anatomical localizations. The aim of this study was to compare the loss of heterozygosity (LOH) by tumor cells by assessing STR profiles of different MM lesions. We examined paired samples of plasma circulating tumor DNA (ctDNA) and CD138+ bone marrow cells in MM patients. For patients with plasmacytomas (66% of 38 patients included), the STR profile of plasmacytomas was also studied when biopsy samples were available. Diverse patterns of LOH were found in lesions of different localization for most patients. LOH in plasma ctDNA, bone marrow, and plasmacytoma samples was found for 55%, 71%, and 100% of patients, respectively. One could expect a greater variety of STR profiles in aberrant loci for patients with plasmacytomas. This hypothesis was not confirmed-no difference in the frequency of LOH in MM patients with or without plasmacytomas was found. This indicates the genetic diversity of tumor clones in MM, regardless of the presence of extramedullar lesions. Therefore, we conclude that risk stratification based on molecular tests performed solely on bone marrow samples may not be sufficient for all MM patients, including those without plasmacytomas. Due to genetic heterogeneity of MM tumor cells from various lesions, the high diagnostic value of liquid biopsy approaches becomes obvious.

Features of Pharmacodynamics of the Anticoagulant Dabigatran in Secondary Thrombophilia.

One of the crucial risk factors for development of severe postthrombotic disease (PTD) is the recurrence of deep vein thrombosis (DVT). New opportunities for pharmacological thromboprophylaxis of secondary thrombophilia were associated with the direct thrombin inhibitor-Dabigatran (Pradaxa; Boehringer Ingelheim, Germany). We aimed to investigate the daily pharmacodynamics of dabigatran in healthy volunteers and patients with PTD. Treatment with dabigatran in patients with PTD having chronic chronometric hypercoagulation and structural hypocoagulation before the administration of the drug is fraught with excessive anticoagulation and a high risk of clinically significant bleeding. In patients with PTD with detected chronometric and structural hypercoagulability before taking a direct thrombin inhibitor, treatment with dabigatran is fraught with possible inadequate anticoagulation and a high risk of clinically significant relapses of thromboses. According to our data, markers of risk of hemorrhagic complications under Dabigatran are the thromboelastography indicators lying within the reference values of the healthy before the administration of the drug: fibrin-platelet clot formation, maximum amplitude of TEG; total lytic activity of blood, and thrombodynamic potential index . Monitoring the effects of the targeted anticoagulant demonstrated the need for correction of dosage and discrete use of the drug in prevention and treatment for thrombohemorrhagic complications in this category of patients. The results of the study prove the efficiency of the therapy with dabigatran and "behavior" of hemostatic potential in patients being taken into account and controlled. Therapy may be long term but requires dynamic monitoring of patients with timely dose adjustment to achieve and maintain the target level of hemostatic potential.