Множественная миелома остается сложным гематологическим заболеванием, требующим постоянного изучения его биологии и поиска новых терапевтических подходов. Несмотря на внедрение в клиническую практику различных классов лекарственных средств, таких как иммуномодулирующие препараты, ингибиторы протеасом и моноклональные антитела, множественная миелома по-прежнему включена в группу хронических неизлечимых заболеваний. Цель настоящей работы – предоставить всесторонний обзор патогенетических механизмов, лежащих в основе лекарственной резистентности, и рассмотреть возможные опции персонализированной терапии. Путем подробного анализа данных клинических исследований последних лет оценить эффективность и возможность применения в клинической практике развивающихся методов лечения. Multiple myeloma (MM) remains a complex hematological disease that requires constant study of its biology and the search for new therapeutic approaches. Despite the introduction into clinical practice of various classes of drugs, such as immunomodulatory drugs, proteasome inhibitors and monoclonal antibodies, MM is still included in the group of chronic incurable diseases. The purpose of this work is to provide a comprehensive overview of the pathogenetic mechanisms underlying drug resistance and to consider possible options for personalized therapy. Through a detailed analysis of data from clinical trials in recent years, to evaluate the effectiveness and feasibility of developing treatment methods in clinical practice.

Aim. To compare the expression levels of the WNT family genes in mesenchymal stromal cells (MSC) of the bone marrow (BM) hematopoietic niche in multiple myeloma (MM) patients vs. healthy donors. Materials & Methods. The study enrolled 12 MM patients aged 49–71 years (the median age 61 years) after standard induction bortezomib therapy. The treatment efficacy was assessed in accordance with the criteria of International Myeloma Working Group (IMWG). Patients were stratified in groups with complete and partial response (CPR; group 1, n = 9) and no response (group 2, n = 3). Besides, a group of primary untreated patients was formed (n = 2). The control group included healthy donors of BM (n = 3). The levels of the WNT and CTNNB1 gene expression were assessed by real-time PCR on cDNA isolated from MSC. Results. In the group of 2 primary patients, two genes (WNT2B and WNT9B) considerably differed in the degree of expression. In non-responders (n = 3), the WNT2B expression could not be determined, whereas the WNT15 expression appeared to be increased. In group CPR (n = 9), mRNA level of the WNT5A gene increased after therapy, whereas the WNT3A gene expression returned to the normal level. The WNT7B gene transcription level did not differ in the control and comparison groups. In group CPR, a significant expression increase in the β-catenin-coding CTNNB1 gene was detected. Conclusion. The differences identified in the expression of the WNT2B, WNT9B, and CTNNB1 genes suggest the possibility of their use as prognostic molecular markers in MM.

Мантийноклеточная лимфома (МКЛ) – агрессивная и тяжело поддающаяся терапии лимфома из зрелых В-лимфоцитов, характеризующаяся транслокацией t(11;14) (q13;q32) и гиперэкспрессией циклина D1. У большинства пациентов заболевание отличается прогрессирующим клиническим течением, требующим незамедлительного начала противоопухолевой терапии, однако наряду с агрессивными вариантами выявляются индолентные МКЛ с длительной выживаемостью и возможностью применения тактики «наблюдай и жди». Такое различие обусловливается наличием вторичных цито- и молекулярно-цитогенетических аберраций, выявляющихся в дополнение к высокоспецифической t(11;14)(q13;q32), которые усиливают онкогенный потенциал циклина D1, вовлекают в лимфомогенез гены, регулирующие клеточный цикл, апоптоз, репарацию поврежденной ДНК, таким образом способствуя увеличению нестабильности генома и дальнейшей злокачественной трансформации опухолевого клона. В настоящее время особое внимание уделяется изучению прогностического влияния изменений кариотипа и аберраций отдельных генов, таких как MYC/8q24 и ТР53/17р13, на выживаемость пациентов с МКЛ. В нашем исследовании мы оценили генетический профиль 117 пациентов с МКЛ для выявления прогностически значимых цитогенетических и молекулярно-генетических маркеров и их взаимосвязи с продолжительностью общей и безрецидивной выживаемости пациентов. Mantle cell lymphoma (MCL) is an aggressive and difficult to treat lymphoma of mature B-lymphocytes characterized by t(11;14)(q13;q32) translocation and overexpression of cyclin D1. In most cases, the disease is manifested by progressive use of therapy, requiring the expense of starting anticancer therapy, however, in combination with aggressive variants, indolent MCL with long-term survival and the possibility of "watch and wait" tactics are detected. This difference is due to the presence of secondary cytogenetic and molecular cytogenetic aberrations, which are revealed in addition to the highly specific translocation t(11;14)(q13;q32), which enhance the oncogenic potential of cyclin D1, involve genes that regulate the cell cycle, apoptosis, and repair in lymphomagenesis. damaged DNA, thus contributing to an increase in genome instability and further malignant transformation of the tumor clone. Currently, special attention is paid to the study of the prognostic impact of changes in the karyotype and aberrations of individual genes, such as MYC/8q24 and TP53/17p13, on the survival of patients with MCL. In our study, we assessed the genetic profile of 117 patients with MCL to identify prognostic cytogenetic and molecular genetic markers and their relationship with the duration of overall and disease-free survival of patients.

Objective: to study the condition of microvascular network in the tissues surrounding the biopsied lymph nodes: in the fat and connective tissue capsule, and to match these findings with the clinical picture of the disease. Material and methods. Our research included 24 patients with Castleman’s disease (CD), all negative for HIV and herpes virus-8 type, at the age of 36–70 years (men-14, women-10). 10 patients had hyaline-vascular type of CD, 14 patients had plasma-cell multicenter type. Of the 24 patients, 10 patients developed POEMS syndrome. The diagnosis of CD was confirmed by the histological examination of the lymph node and immunohistochemical study of the distribution of B- and T- lymphocytes in the node tissue. Vessels showed immunohistochemical positivity with antibodies to CD34, plasma cells with antibodies to CD138. Four patients with POEMS syndrome did not receive treatment, 6 patients received various types of therapy. Of these, 2 patients underwent therapy with autologous stem cell transplantation of bone marrow. Both patients were in remission of CD and POEMS for 10 years. Two patients received 5 cycles of therapy according to VCD scheme. They were alive for 5 years with the reduction of POEMS’s symptoms. 1 patient with POEMS and autoimmune hemolysis has received 10 courses of R-CHOP and has resulted in remission for 3 years. Two of the 6 deceased patients with POEMS syndrome underwent autopsy. Results and discussion. In all patients, regardless of the histological variant of CD, productive vasculitis in microvascular network was found and it had following characteristics: thickening of the walls due to lymph-histiocytic infiltration, fibrosis, swelling of endothelial cells, which narrowed or completely obstruct the vessel’s lumen. The most severe sclerosis of small vessels in the lymph node tissue was observed in patients with POEMS, in which perivascular infiltration included plasma cells. Patients with POEMS showed extensive involvement in the sclerotic process nearby vessels. The study of the microvascular network on the autopsy material revealed its systemic damage in all internal organs. Conclusion. Regardless of the histological variant of Castleman’s disease, in all 24 cases there was a lesion of microvascular network in the form of plasma cell productive vasculitis, with the most severe changes in group of patients with POEMS syndrome.

В лекции рассмотрены отдельные аспекты трансплантации аллогенных и аутологичных гемопоэтических стволовых клеток больным онкогематологическими заболеваниями.