Вопросы гематологии/онкологии и иммунопатологии в педиатрии. 2025; 24: 167-174
Острый миелоидный лейкоз с транслокациями, вовлекающими ген КМТ2А, у близнецов как модель для исследования лейкемогенеза: описание клинических случаев и генетические характеристики
https://doi.org/10.24287/1726-1708-2025-24-1-167-174Аннотация
Семейные случаи острых лейкозов у детей встречаются очень редко и главным образом описаны в рамках генетически детерминированных синдромов предрасположенности (мутации в генах RUNX1, ETV6, ANKRD26, GATA2, SAMD9/SAMD9L, CEBPA), которые хорошо охарактеризованы за последние 15 лет. Лейкозы у близнецов встречаются еще реже и представляют особый интерес с точки зрения изучения закономерностей лейкемогенеза и эволюции лейкемических субклонов. В данной работе мы приводим описание трех пар близнецов с различными сценариями развития/неразвития острого лейкоза: в одной паре КМТ2А-r-ассоциированный лейкоз был диагностирован одновременно, в двух других второй ребенок остается здоровым, несмотря на развитие КМТ2А-r-ассоциированного лейкоза у близнеца. Родители пациентов дали согласие на использование информации, в том числе фотографий детей, в научных исследованиях и публикациях.
Список литературы
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21. Калинина И.И., Венёв Д.А., Ольшанская Ю.В., Садовская М.Н., Горонкова О.В., Салимова Т.Ю. и др. Результаты терапии детей с острым миелоидным лейкозом, получивших терапию по протоколу ОМЛ-ММ-2006. Вопросы гематологии/онкологии и иммунопатологии в педиатрии. 2022; 21 (1): 20–35. DOI: 10.24287/1726-1708-2022-21-1-20-35
Pediatric Hematology/Oncology and Immunopathology. 2025; 24: 167-174
Acute myeloid leukemia with translocations involving the KMT2A gene in twins as a model for the study of leukemogenesis: clinical case reports and genetic characteristics
https://doi.org/10.24287/1726-1708-2025-24-1-167-174Abstract
Familial cases of acute leukemia in children are very rare and are mainly reported in cases of genetically determined predisposition syndromes (mutations in the RUNX1, ETV6, ANKRD26, GATA2, SAMD9/SAMD9L, CEBPA genes) which have been well characterized in the last 15 years. In twins, leukemia is even more rare and is of particular interest for the study of leukemogenesis patterns and evolution of leukemic subclones. Here, we report about three pairs of twins: in one pair, KMT2A-r-leukemia was diagnosed simultaneously, while in the other two cases the second child remained healthy despite the development of KMT2A-r-leukemia in their twin. The patients’ parents gave consent to the use of their children's data, including photographs, for research purposes and in publications.
References
1. Tarlock K., Cooper T.M. Acute myeloid leukemia in children and adolescents. In: UpToDate, Julie R. Park (ed.), Wolters Kluwer. (Accessed on Oct 26, 2023.)
2. Gill P., Lende M.N., Van Hook J.W. Twin Births. 2023 Feb 6. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2023.
3. Wolman I.J. Parallel responses to chemotherapy in identical twin infants with concordant leukemia. J Pediatr 1962; 60: 91–5. DOI: 10.1016/s0022-3476(62)80014-6
4. Greaves M.F., Maia A.T., Wiemels J.L., Ford A.M. Leukemia in twins: lessons in natural history. Blood 2003; 102 (7): 2321–33. DOI: 10.1182/blood-2002-12-3817
5. Falletta J.M., Starling K.A., Fernbach D.J. Leukemia in twins. Pediatrics 1973; 52 (6): 846–9.
6. Khera S., Kurup A., Agarwal S., Tripathi P. Synchronous presentation of ETV6::RUNX1 fusion positive concordant B-acute lymphoblastic leukaemia in identical twin toddlers. BMJ Case Rep 2023; 16: e257139.
7. Tebbi C.K. Etiology of Acute Leukemia: A Review. Cancers (Basel) 2021; 13 (9): 2256. DOI: 10.3390/cancers13092256
8. Zipf T.F., Berg S., Roberts W.M., Poplack D.G., Steuber C.P., Bleyer W.A. Childhood Leukemias. In: Abeloff M.D., Armitage J.O., Lichter A.S., Niederhuber J.E. (eds.). Clinical Oncology. 2nd ed. Philadelphia: Churchill Livingston; 2000. Rr. 2402–24.
9. Ford A.M., Greaves M. ETV6-RUNX1 + Acute Lymphoblastic Leukaemia in Identical Twins. Adv Exp Med Biol 2017; 962: 217–28. DOI: 10.1007/978-981-10-3233-2_14
10. Ford A.M., Colman S., Greaves M. Covert pre-leukaemic clones in healthy co-twins of patients with childhood acute lymphoblastic leukaemia. Leukemia 2023; 37 (1): 47–52. DOI: 10.1038/s41375-022-01756-1
11. Liao X.Y., Fang J.P., Zhou D.H., Qiu K.Y. CEBPA are independent good prognostic factors in pediatric acute myeloid leukemia. Hematol Oncol 2022; 40 (2): 258–68. DOI: 10.1002/hon.2951
12. Su L., Shi Y.Y., Liu Z.Y., Gao S.J. Acute Myeloid Leukemia with CEBPA Mutations: Current Progress and Future Directions. Front Oncol 2022; 12: 806137. DOI: 10.3389/fonc.2022.806137
13. Debeljak M., Kitanovski L., Pajič T., Jazbec J. Concordant acute myeloblastic leukemia in monozygotic twins with germline and shared somatic mutations in the gene for CCAAT-enhancer-binding protein a with 13 years difference at onset. Haematologica 2013; 98 (7): e73–4. DOI: 10.3324/haematol.2012.082578
14. Foster J.H., Williams C.L., Elghetany M.T., Liu P., Krance R.A., Bertuch A.A., Gramatges M.M. Monozygotic twins with non-Down syndrome associated MLL-rearranged hematologic malignancy and megakaryoblastic differentiation. Leuk Lymphoma 2019; 60 (4): 1083–6. DOI: 10.1080/10428194.2018.1516883
15. Jimenez-Antolinez Y.V., Gonzalez-Lopez E.E., Ruiz I.Y.V., Cantu-Moreno M., Gomez-Almaguer D., Gonzalez-Llano O. Concordant acute myeloblastic leukemia in identical twins treated with allogeneic transplantation from a younger HLA-identical sibling following a single apheresis procedure. Int J Hematol Oncol 2020; 10 (1): IJH32. DOI: 10.2217/ijh-2020-0017
16. Ng R.K., Kong C.T., So C.C., Lui W.C., Chan Y.F., Leung K.C., et al. Epigenetic dysregulation of leukaemic HOX code in MLL-rearranged leukaemia mouse model. J Pathol 2014; 232 (1): 65–74. DOI: 10.1002/path.4279
17. Andersson A.K., Ma J., Wang J., Chen X., Gedman A.L., Dang J., et al.; St. Jude Children's Research Hospital–Washington University Pediatric Cancer Genome Project. The landscape of somatic mutations in infant MLL-rearranged acute lymphoblastic leukemias. Nat Genet 2015; 47 (4): 330–7. DOI: 10.1038/ng.3230
18. Meyer C., Larghero P., Almeida Lopes B., Burmeister T., Gröger D., Sutton R., et al. The KMT2A recombinome of acute leukemias in 2023. Leukemia 2023; 37 (5): 988–1005. DOI: 10.1038/s41375-023-01877-1
19. Nilson I., Löchner K., Siegler G., Greil J., Beck J.D., Fey G.H., Marschalek R. Exon/intron structure of the human ALL-1 (MLL) gene involved in translocations to chromosomal region 11q23 and acute leukaemias. Br J Haematol 1996; 93 (4): 966–72. DOI: 10.1046/j.1365-2141.1996.d01-1748.x
20. Kalinina I.I., Maschan A.A., Ol'shanskaya Yu.V., Tsaur G.A., Dubrovina M.E., Popov A.M. i dr. Diagnostika i lechenie ostrogo mieloidnogo leikoza u detei. Uchebnoe posobie. M.; 2021. 104 s.
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