medgenМедицинская генетикаMedical Genetics2073-7998Publishing House «Genius Media» LLC10.25557/2073-7998.2018.06.39-47medgen-499Research ArticleОРИГИНАЛЬНЫЕ ИССЛЕДОВАНИЯORIGINAL RESEARCHАномалии хромосом 5, 7, 11 и 17 в комплексном кариотипе при миелодиспластических синдромах и острых миелоидных лейкозахAnomalies of chromosomes 5, 7, 11 and 17 with complex karyotype in myelodysplastic syndrome and acute myeloid leukemia patientsГребенюкЛ. А.GrebenyukL. A.noemail@neicon.ruОбуховаТ. Н.ObukhovaT. N.noemail@neicon.ruПаровичниковаЕ. Н.AlimovaG. A.noemail@neicon.ruАлимоваГ. А.ShishiginaL. A.noemail@neicon.ruШишигинаЛ. А.TroitskayaV. V.noemail@neicon.ruТроицкаяВ. В.KokhnoA. V.noemail@neicon.ruКохноА. В.ParovichnikovaE. N.noemail@neicon.ruСавченкоВ. Г.SavchenkoV. G.noemail@neicon.ruФГБУ «Национальный медицинский исследовательский центр гематологии» Министерства здравоохранения Российской ФедерацииРоссияNational Research Center for HematologyRussian Federation2018060920181763947Copyright © Гребенюк Л.А., Обухова Т.Н., Паровичникова Е.Н., Алимова Г.А., Шишигина Л.А., Троицкая В.В., Кохно А.В., Савченко В.Г., 20182018Гребенюк Л.А., Обухова Т.Н., Паровичникова Е.Н., Алимова Г.А., Шишигина Л.А., Троицкая В.В., Кохно А.В., Савченко В.Г.Grebenyuk L.A., Obukhova T.N., Alimova G.A., Shishigina L.A., Troitskaya V.V., Kokhno A.V., Parovichnikova E.N., Savchenko V.G.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.medgen-journal.ru/jour/article/view/499

Комплексный кариотип (КК) у больных миелодиспластическими синдромами (МДС) и острыми миелоидными лейкозами (ОМЛ) является фактором неблагоприятного прогноза, связан с высокой частотой рефрактерных форм и рецидивов. При стандартном цитогенетическом исследовании (СЦИ) идентификация хромосомных аномалий в КК затруднена в связи с низкой разрешающей способностью метода. Молекулярно-цитогенетические методы - iFISH, mFISH, mBAND, позволяют идентифицировать сложные и субмикроскопические хромосомные перестройки, маркерные хромосомы и уточнять точки разрыва хромосом. Этими методами охарактеризованы КК 15 больных МДС и 11 ОМЛ. mFISH и iFISH выполнены всем 26 больным, mBAND выполнен в двух случаях. При СЦИ выявлено в среднем 7 аномалий кариотипа (3-21). Структурные аномалии выявлены во всех случаях (n = 26): реципрокные транслокации (38,4%), делеции (65,3%), дополнительный хромосомный материал неизвестного происхождения (69,2%), маркерные хромосомы (53,8%). Обнаружены числовые аномалии типичные для МДС и ОМЛ (n = 26): трисомия 8 (15,3%), моносомии 5 (42,3%), 7 (34,6%) и 17 (11,5%). Молекулярно-цитогенетические методы выявили дополнительные аномалии и/или дополнительные точки разрыва хромосом в 19 случаях. Выявлены транслокации: реципрокные - 22 случая, сложные - 13 случаев. У 23 пациентов обнаружены аномалии хромосом 5 (76,9%), 7 (57,6%), 11 (34,6%) и 17 (46,1%). Подтверждены делеция 5q в пяти случаях, делеция 7q в одном случае. Истинная моносомия 7 подтверждена в одном случае. Остальные случаи моносомии 5, 7 и 17 молекулярно-цитогенетическими методами идентифицированы как транслокации с делециями локусов 5q31, 7q31 и 17p13. Все маркерные хромосомы и дополнительный неидентифицируемый хромосомный материал распознаны как сложные транслокации или деривативные хромосомы. Сочетание стандартного и молекулярно-цитогенетических методов исследования необходимо для полной характеристики комплексных кариотипов при МДС и ОМЛ и определения точек разрыва хромосом в локусах потенциальных онкогенов и генов супрессоров опухолевого роста.

Complex karyotype (CK) in patients with myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML) is a factor of unfavorable prognosis, associated with high frequency of refractory forms and relapses. Precise identification of chromosome abnormalities in CK by conventional cytogenetic analysis (CCA) is limited due to low resolution of this method. Molecular cytogenetic techniques (FISH, mFISH, mBAND) have significantly higher sensitivity and allow to identify complex chromosome abnormalities, marker chromosomes, submicroscopic deletions and specify chromosomes breakpoints. This study included 15 MDS and 11 AML patients whose complex karyotypes were characterized by these methods. mFISH and iFISH are performed in all 26 patients, mBAND is performed in two cases. CCA revealed an average of 7 karyotype abnormalities (from 3 to 21). Structural rearrangements were found in all cases (n = 26): reciprocal translocations (38.4%), deletions (65.3%), additional chromosomal material of unknown origin (69.2%), marker chromosomes (53.8%). Numerical anomalies typical for MDS and AML (n = 26) were found: trisomy 8 (15.3%), monosomy 5 (42.3%), 7 (34.6%) and 17 (11.5%). Molecular cytogenetic analysis revealed additional chromosomal abnormalities and / or additional chromosome breakpoints in 19 cases. Translocations were found: reciprocal in 22 cases, complicated in 13 cases. In karyotype of 23 patients we found chromosome anomalies 5 (76.9%), 7 (57.6%), 11 (34.6%) and 17 (46.1%). The deletion 5q was confirmed in five cases, the deletion of 7q in one case. True monosomy 7 is confirmed in one case. On the results of molecular cytogenetic techniques in all other cases with monosomy 5, 7, and 17 revealed fragments of these chromosomes involved in translocations were combined deletions of loci 5q31, 7q31 and 17p13. All marker chromosomes and chromosomes with additional material of unknown origin were recognized as complex translocations or derivative chromosomes with breakpoints in both arms. Combination of CCA and molecular cytogenetic techniques is necessary for the complete characterization of complex karyotypes in MDS and AML and for precise for characteristic of CK in MDS and AML and determination of exact breakpoints loci of potential oncogenes and tumor suppressor genes.

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The authors declare that there are no conflicts of interest present.