MD-OncoMD-OncoMD-Onco2782-32022782-6171Publishing House ABV Press24410.17650/2782-3202-2026-6-2-90-98LITERATURE REVIEWОБЗОР ЛИТЕРАТУРЫReview ArticleSpecific features of hematologic tumors in children with hereditary genetic syndromesОсобенности опухолевых заболеваний системы крови у детей с наследственными генетическими синдромами (обзор литературы)https://orcid.org/0009-0008-2603-773XArtemovaV. D.АртемоваВ. Д.
Russian Federation
valeryartemova2011@gmail.comhttps://orcid.org/0000-0002-1469-2365ValievT. T.ВалиевТ. Т.
Russian Federation
valeryartemova2011@gmail.comI.M. Sechenov First Moscow State Medical University, Ministry of Health of Russia (Sechenov University)ФГАОУ ВО Первый Московский государственный медицинский университет им. И.М. Сеченова Минздрава России (Сеченовский Университет)N.N. Blokhin National Medical Research Center of Oncology, Ministry of Health of RussiaФГБУ «Национальный медицинский исследовательский центр онкологии им. Н.Н. Блохина» Минздрава РоссииRussian Medical Academy of Continuing Professional Education, Ministry of Health of RussiaФГБОУ ДПО «Российская медицинская академия непрерывного профессионального образования» Минздрава России210820266290982108202621082026Copyright ©; 2026, ABV-PressCopyright ©; 2026, АБВ-пресс2026ABV-PressАБВ-прессhttps://creativecommons.org/licenses/by/4.0/https://mdonco.abvpress.ru/jour/article/view/244

Hereditary genetic syndromes are a significant risk factor for development of oncohematological diseases in childhood. Specifically, Down syndrome is associated with a 500-fold increased risk of acute megakaryoblastic leukemia and a 20-fold increased risk of acute lymphoblastic leukemia compared to the general population. The pathogenesis of leukemia in various hereditary syndromes involves three key mechanisms: impaired DNA repair (as seen in Fanconi anemia, Bloom syndrome), congenital genomic instability (characteristic of ataxia-telangiectasia, Li–Fraumeni, Nijmegen breakage syndrome), and constitutive activation of proliferative signaling pathways (RAS/MAPK pathway in Noonan syndrome and neurofibromatosis type 1).

Specificities of pathogenesis explain therapeutic responses and recommended options in this group of patients. For patients with genomic instability syndromes and bone marrow failure syndromes a 50 % dose reduction of chemotherapeutic agents, complete avoidance of alkylating agents, and exclusion of radiotherapy are recommended. Allogeneic hematopoietic stem cell transplantation remains the only curative treatment option but requires modified conditioning regimens. Contemporary fludarabine-based hematopoietic stem cell transplantation protocols achieve 83 % 5-year survival in Fanconi anemia patients. Emerging innovative therapies (PARP inhibitors, JAK-kinase inhibitors, blinatumomab, tisagenlecleucel) represent promising strategies to enhance treatment efficacy while reducing toxicity.

Наследственные генетические синдромы – значимый фактор риска развития онкогематологических заболеваний в детском возрасте. Так, риск острого мегакариобластного лейкоза у больных синдромом Дауна повышается в 500 раз, а острого лимфобластного лейкоза – в 20 раз по сравнению с общей популяцией. Ключевыми универсальными патогенетическими механизмами лейкозогенеза при различных наследственных синдромах являются нарушение репарации ДНК (синдромы Фанкони, Блума), врожденная геномная нестабильность (атаксия-телеангиэктазия, синдромы Ли–Фраумени, Ниймеген) и конституциональная активация пролиферативных сигнальных путей (RAS/MAPK при синдроме Нунан и нейрофиброматозе 1-го типа).

Особенности патогенеза объясняют ответ на терапию и рекомендованные терапевтические опции в данной группе пациентов. Для пациентов с синдромами геномной нестабильности и костномозговой недостаточности важны снижение доз химиопрепаратов на 50 %, полное исключение алкилирующих агентов и лучевой терапии из программ лечения. Применение аллогенной трансплантации гемопоэтических стволовых клеток остается единственным радикальным методом лечения, однако требует использования модифицированных режимов кондиционирования. При анемии Фанкони современные протоколы аллогенной трансплантации гемопоэтических стволовых клеток с флударабином обеспечивают 5-летнюю выживаемость на уровне 83 %. Перспективным направлением является использование инновационных препаратов (ингибиторы PARP, JAK-киназ, блинатумомаб, тисагенлеклейцел), позволяющих улучшить результаты и снизить токсичность лечения.

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