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<article xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" xmlns:ali="http://www.niso.org/schemas/ali/1.0/" article-type="other" dtd-version="1.2" xml:lang="en"><front><journal-meta><journal-id journal-id-type="publisher-id">Oncohematology</journal-id><journal-title-group><journal-title xml:lang="en">Oncohematology</journal-title><trans-title-group xml:lang="ru"><trans-title>Онкогематология</trans-title></trans-title-group></journal-title-group><issn publication-format="print">1818-8346</issn><issn publication-format="electronic">2413-4023</issn><publisher><publisher-name xml:lang="en">Publishing House ABV Press</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="publisher-id">1052</article-id><article-id pub-id-type="doi">10.17650/1818-8346-2025-20-3-52-59</article-id><article-categories><subj-group subj-group-type="toc-heading" xml:lang="en"><subject>CURRENT BASIC RESEARCH IN HEMATOLOGY AND PRACTICAL MEDICINE</subject></subj-group><subj-group subj-group-type="toc-heading" xml:lang="ru"><subject>ФУНДАМЕНТАЛЬНЫЕ ИССЛЕДОВАНИЯ В ОНКОГЕМАТОЛОГИИ И ПРАКТИЧЕСКОЙ МЕДИЦИНЕ НА СОВРЕМЕННОМ ЭТАПЕ</subject></subj-group><subj-group subj-group-type="article-type"><subject></subject></subj-group></article-categories><title-group><article-title xml:lang="en">c-MAF protein expression in multiple myeloma</article-title><trans-title-group xml:lang="ru"><trans-title>Экспрессия белка c-MAF при множественной миеломе</trans-title></trans-title-group></title-group><contrib-group><contrib contrib-type="author"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0003-4142-171X</contrib-id><name-alternatives><name xml:lang="en"><surname>Solov’eva</surname><given-names>M. V.</given-names></name><name xml:lang="ru"><surname>Соловьева</surname><given-names>М. В.</given-names></name></name-alternatives><address><country country="RU">Russian Federation</country></address><bio xml:lang="en"><p>Maya Valer’evna Solov’eva</p><p>4 Novyy Zykovskiy Proezd, Moscow 12516</p></bio><bio xml:lang="ru"><p>Майя Валерьевна Соловьева</p><p>125167 Москва, Новый Зыковский пр-д, 4</p></bio><email>solomaiia@yandex.ru</email><xref ref-type="aff" rid="aff1"/></contrib><contrib contrib-type="author"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0002-7944-6202</contrib-id><name-alternatives><name xml:lang="en"><surname>Solov’ev</surname><given-names>M. V.</given-names></name><name xml:lang="ru"><surname>Соловьев</surname><given-names>М. В.</given-names></name></name-alternatives><address><country country="RU">Russian Federation</country></address><bio xml:lang="en"><p>4 Novyy Zykovskiy Proezd, Moscow 12516</p></bio><bio xml:lang="ru"><p>125167 Москва, Новый Зыковский пр-д, 4</p></bio><xref ref-type="aff" rid="aff1"/></contrib><contrib contrib-type="author"><contrib-id contrib-id-type="orcid">https://orcid.org/0009-0003-1694-6861</contrib-id><name-alternatives><name xml:lang="en"><surname>Melnikova</surname><given-names>M. V.</given-names></name><name xml:lang="ru"><surname>Мельникова</surname><given-names>М. В.</given-names></name></name-alternatives><address><country country="RU">Russian Federation</country></address><bio xml:lang="en"><p>4 Novyy Zykovskiy Proezd, Moscow 125167</p></bio><bio xml:lang="ru"><p>125167 Москва, Новый Зыковский пр-д, 4</p></bio><xref ref-type="aff" rid="aff1"/></contrib><contrib contrib-type="author"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0002-1082-8659</contrib-id><name-alternatives><name xml:lang="en"><surname>Kovrigina</surname><given-names>A. M.</given-names></name><name xml:lang="ru"><surname>Ковригина</surname><given-names>А. М.</given-names></name></name-alternatives><address><country country="RU">Russian Federation</country></address><bio xml:lang="en"><p>4 Novyy Zykovskiy Proezd, Moscow 125167</p></bio><bio xml:lang="ru"><p>125167 Москва, Новый Зыковский пр-д, 4</p></bio><xref ref-type="aff" rid="aff1"/></contrib><contrib contrib-type="author"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0003-1613-652X</contrib-id><name-alternatives><name xml:lang="en"><surname>Obukhova</surname><given-names>T. N.</given-names></name><name xml:lang="ru"><surname>Обухова</surname><given-names>Т. Н.</given-names></name></name-alternatives><address><country country="RU">Russian Federation</country></address><bio xml:lang="en"><p>4 Novyy Zykovskiy Proezd, Moscow 125167</p></bio><bio xml:lang="ru"><p>125167 Москва, Новый Зыковский пр-д, 4</p></bio><xref ref-type="aff" rid="aff1"/></contrib><contrib contrib-type="author"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0002-4966-8146</contrib-id><name-alternatives><name xml:lang="en"><surname>Mendeleeva</surname><given-names>L. P.</given-names></name><name xml:lang="ru"><surname>Менделеева</surname><given-names>Л. П.</given-names></name></name-alternatives><address><country country="RU">Russian Federation</country></address><bio xml:lang="en"><p>4 Novyy Zykovskiy Proezd, Moscow 125167</p></bio><bio xml:lang="ru"><p>125167 Москва, Новый Зыковский пр-д, 4</p></bio><xref ref-type="aff" rid="aff1"/></contrib></contrib-group><aff-alternatives id="aff1"><aff><institution xml:lang="en">National Medical Research Center for Hematology, Ministry of Health of Russia</institution></aff><aff><institution xml:lang="ru">ФГБУ «Национальный медицинский исследовательский центр гематологии» Минздрава России</institution></aff></aff-alternatives><pub-date date-type="pub" iso-8601-date="2025-09-11" publication-format="electronic"><day>11</day><month>09</month><year>2025</year></pub-date><volume>20</volume><issue>3</issue><issue-title xml:lang="en"/><issue-title xml:lang="ru"/><fpage>52</fpage><lpage>59</lpage><history><date date-type="received" iso-8601-date="2025-09-10"><day>10</day><month>09</month><year>2025</year></date><date date-type="accepted" iso-8601-date="2025-09-10"><day>10</day><month>09</month><year>2025</year></date></history><permissions><ali:free_to_read xmlns:ali="http://www.niso.org/schemas/ali/1.0/"/></permissions><self-uri xlink:href="https://oncohematology.abvpress.ru/ongm/article/view/1052">https://oncohematology.abvpress.ru/ongm/article/view/1052</self-uri><abstract xml:lang="en"><p><bold>Background</bold>. The c-MAF oncogene, located in the 16q23.2 region, encodes the protein of the same name, a transcription factor whose role continues to be studied. Given the activating effect of the c-MAF transcription factor in enhancing the interaction between the tumor cell and the bone marrow stroma, we hypothesized that c-MAF protein expression would be more frequently detected in multiple myeloma (MM) patients without plasmacytomas.Aim. To analyze the c-MAF protein expression pattern in bone marrow trephine biopsy specimens of patients with newly diagnosed MM with and without plasmacytomas.<bold>Materials and methods</bold>. The retrospective single-center study included 31 patients (7 men and 24 women) with newly diagnosed MM aged 29 to 78 years (median – 55 years). The first cohort of patients included 12 patients with t(14;16), the second cohort – 19 patients without this translocation. In 21 patients, plasmacytomas were not detected at the disease onset, in 10 patients, bone or extramedullary plasmacytomas were detected. Low-dose body computed tomography was used to detect bone lesions. The diagnosis was established in accordance with the International Myeloma Working Group 2014 criteria. Positive immunomagnetic selection of CD138+ bone marrow cells was performed using a monoclonal antibody to CD138 (Miltenyi Biotec, Germany) according to the manufacturer’s protocol. Fluorescent hybridization in situ of CD138+ cells was performed using DNA probes to detect translocations 14q32 / IgH, 8q24 / MYC, deletions 17p13 / TP53, 13q14, 1p32, amplification of 1q21 (amp1q21) and multiple trisomies (MetaSystems, Germany). High-risk cytogenetic aberrations included t(14;16), t(4;14), del17p13, amp1q21. Immunohistochemical examination of bone marrow trephine biopsy specimens using c-MAF antibody was performed in all patients. A heterogeneous or monomorphic nuclear reaction in more than 10 % of the tumor plasma cells was considered as positive c-MAF protein expression.<bold>Results</bold>. Cytogenetic examination of CD138+ bone marrow cells revealed high-risk aberrations in 24 patients, and standard risk cytogenetics was diagnosed in seven patients. c-MAF protein expression was detected in 29 % (6 of 21) of patients without plasmacytomas and in 70 % (7 of 10) of patients with plasmacytomas. c-MAF protein expression was strongly correlated with t(14;16) presence. In cases where it was absent, c-MAF protein expression in bone marrow was not observed, with the exception of one case. Thus, c-MAF protein expression in bone marrow was noted in 13 patients – twelve with t(14;16) and one patient with double hit myeloma (del17p13 and t(4;14)). No relationship was found between c-MAF protein expression and the presence / absence of plasmacytomas. In the presence of t(14;16), an atypical distribution of patients by paraprotein type was noted (immunoglobulins G, A, BJ myeloma occurred with the same frequency – 33.3 %). In MM with t(14;16), a tendency to more frequent detection of plasma cells in the peripheral blood was found (29 %); a quarter of patients had kidney damage. Plasmacytomas were detected in 50 % of patients with t(14;16), and in 25 % of them – extramedullary. Most patients with t(14;16) had stage III according to International Staging System (82 %).<bold>Conclusion</bold>. The expression of c-MAF protein strongly correlated with t(14;16) presence, however, no correlation with the presence / absence of plasmacytomas could be found. MM with t(14;16) is characterized by an aggressive phenotype. In the presence of t(14;16), there is a tendency towards a high frequency of kidney damage, detection of extramedullary plasmacytomas and plasma cells in the peripheral blood, and diagnosis at advanced stages of the disease.</p></abstract><trans-abstract xml:lang="ru"><p><bold>Введение</bold>. Онкоген с-MAF, расположенный в регионе 16q23.2, кодирует одноименный белок – транскрипционный фактор, роль которого продолжает изучаться. Учитывая активирующий эффект транскрипционного фактора c-MAF в усилении взаимодействия между опухолевой клеткой и стромой костного мозга, мы предположили, что экспрессия белка c-MAF будет чаще обнаружена у больных множественной миеломой (ММ) без плазмоцитом.<bold>Цель исследования</bold> – проанализировать характер экспрессии белка c-MAF в трепанобиоптате костного мозга больных впервые диагностированной ММ с плазмоцитомами и без них.<bold>Материалы и методы</bold>. В ретроспективное одноцентровое исследование включен 31 пациент (7 мужчин и 24 женщины) с впервые диагностированной ММ в возрасте 29–78 лет (медиана – 55 лет). Первая когорта включала 12 пациентов с t(14;16), вторая – 19 больных без этой транслокации. У 21 пациента в дебюте заболевания плазмоцитомы не обнаружены, у 10 выявлялись костные или экстрамедуллярные плазмоцитомы. Для детекции поражения костей применяли низкодозную компьютерную томографию тела. Диагноз устанавливали в соответствии с критериями Международной рабочей группы по миеломе (2014). Проведена положительная иммуномагнитная селекция CD138+-клеток костного мозга с использованием моноклонального антитела к CD138 (Miltenyi Biotec, Германия) согласно протоколу производителя. Выполнено исследование CD138+-клеток методом флуоресцентной гибридизации in situ с использованием ДНК-зондов для выявления транслокаций 14q32 / IgH, 8q24 / MYC, делеций 17р13 / ТР53, 13q14, 1p32, амплификации 1q21 (amp1q21) и множественных трисомий (MetaSystems, Германия). К цитогенетическим аберрациям высокого риска относили t(14;16), t(4;14), del17p13, amp1q21. Всем пациентам проведено иммуногистохимическое исследование трепанобиоптата костного мозга с применением антитела к c-MAF. Гетерогенную или мономорфную ядерную реакцию более чем в 10 % плазматических клеток опухолевого субстрата расценивали как положительную экспрессию белка c-MAF.<bold>Результаты</bold>. У 24 больных при цитогенетическом исследовании CD138+-клеток костного мозга выявлены аберрации высокого риска, у 7 пациентов диагностирован стандартный цитогенетический риск. Экспрессия белка c-MAF выявлена у 29 % (6 из 21) больных без плазмоцитом и у 70 % (7 из 10) больных с плазмоцитомами. Экспрессия белка c-MAF строго коррелировала с наличием t(14;16). Если таковая отсутствовала, экспрессии белка c-MAF в костном мозге не отмечалось за исключением 1 случая. Таким образом, экспрессия белка c-MAF в костном мозге отмечена у 13 больных: у 12 с t(14;16) и у 1 с double hit миеломой (del17p13 и t(4;14)). Зависимости между экспрессией белка c-MAF и наличием / отсутствием плазмоцитом не выявлено. При t(14;16) отмечено нехарактерное распределение больных по типу парапротеина (иммуноглобулины G, A, миелома BJ встречались с одинаковой частотой – 33,3 %). При ММ, протекающей с t(14;16), обнаружена тенденция к более частому выявлению плазматических клеток в периферической крови (29 %), у четверти больных отмечено поражение почек. Плазмоцитомы выявлены у 50 % пациентов с t(14;16), у 25 % из них – экстрамедуллярные. У превалирующего большинства больных с t(14;16) зафиксирована III стадия по Международной системе стадирования (82 %).<bold>Заключение</bold>. Экспрессия белка с-MAF строго коррелировала с присутствием t(14;16), вместе с тем корреляции с наличием / отсутствием плазмоцитом выявить не удалось. ММ, протекающая с t(14;16), характеризуется агрессивным фенотипом. При t(14;16) отмечается тенденция к высокой частоте поражения почек, детекции экстрамедуллярных плазмоцитом и плазматических клеток в периферической крови, диагностике на распространенных стадиях болезни.</p></trans-abstract><kwd-group xml:lang="en"><kwd>multiple myeloma</kwd><kwd>t(14</kwd><kwd>16)</kwd><kwd>fluorescent hybridization in situ of CD138+ cells</kwd><kwd>c-MAF oncogene</kwd><kwd>c-MAF protein</kwd><kwd>plasmacytoma</kwd><kwd>immunohistochemical study</kwd></kwd-group><kwd-group xml:lang="ru"><kwd>множественная миелома</kwd><kwd>t(14</kwd><kwd>16)</kwd><kwd>исследование CD138+-клеток методом флуоресцентной гибридизации in situ</kwd><kwd>онкоген с-MAF</kwd><kwd>белок c-MAF</kwd><kwd>плазмоцитома</kwd><kwd>иммуногистохимическое исследование</kwd></kwd-group><funding-group/></article-meta></front><body></body><back><ref-list><ref id="B1"><label>1.</label><mixed-citation>Nakayama T., Hieshima K., Izawa D. et al. 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