<?xml version="1.0" encoding="UTF-8"?>
<!DOCTYPE root>
<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">Pediatric Hematology/Oncology and Immunopathology</journal-id><journal-title-group><journal-title xml:lang="en">Pediatric Hematology/Oncology and Immunopathology</journal-title><trans-title-group xml:lang="ru"><trans-title>Вопросы гематологии/онкологии и иммунопатологии в педиатрии</trans-title></trans-title-group></journal-title-group><issn publication-format="print">1726-1708</issn><issn publication-format="electronic">2414-9314</issn><publisher><publisher-name xml:lang="en">Fund Doctors, Innovations, Science for Children</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="publisher-id">780</article-id><article-id pub-id-type="doi">10.24287/1726-1708-2024-23-1-56-62</article-id><article-categories><subj-group subj-group-type="toc-heading" xml:lang="en"><subject>ORIGINAL ARTICLES</subject></subj-group><subj-group subj-group-type="toc-heading" xml:lang="ru"><subject>ОРИГИНАЛЬНЫЕ СТАТЬИ</subject></subj-group><subj-group subj-group-type="article-type"><subject></subject></subj-group></article-categories><title-group><article-title xml:lang="en">The prognostic value of <italic>TP53</italic> mutational status in children with Burkitt lymphoma treated according to the B-NHL-2010M protocol</article-title><trans-title-group xml:lang="ru"><trans-title>Прогностическое значение статуса гена <italic>TP53</italic> у детей с лимфомой Беркитта на протоколе В-НХЛ-2010М</trans-title></trans-title-group></title-group><contrib-group><contrib contrib-type="author"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0002-2574-1636</contrib-id><name-alternatives><name xml:lang="en"><surname>Volchkov</surname><given-names>E. V.</given-names></name><name xml:lang="ru"><surname>Волчков</surname><given-names>Е. В.</given-names></name></name-alternatives><address><country country="RU">Russian Federation</country></address><bio xml:lang="en"><p>Egor V. Volchkov, a hematologist</p><p>Lymphoma Research Department</p><p>117997; 1 Samory Mashela St.; Moscow</p></bio><bio xml:lang="ru"><p>Егор Васильевич Волчков, врач-гематолог</p><p>отдел исследования лимфом</p><p>117997; ул. Саморы Машела, 1; Москва</p></bio><email>volchcov.egor@yandex.ru</email><xref ref-type="aff" rid="aff1"/><xref ref-type="aff" rid="aff2"/></contrib><contrib contrib-type="author"><name-alternatives><name xml:lang="en"><surname>Abugova</surname><given-names>Yu. G.</given-names></name><name xml:lang="ru"><surname>Абугова</surname><given-names>Ю. Г.</given-names></name></name-alternatives><address><country country="RU">Russian Federation</country></address><bio xml:lang="en"><p>Moscow</p></bio><bio xml:lang="ru"><p>Юлия Георгиевна Абугова</p><p>Москва</p></bio><email>Yuliya.Abugova@fccho-moscow.ru</email><xref ref-type="aff" rid="aff1"/></contrib><contrib contrib-type="author"><name-alternatives><name xml:lang="en"><surname>Brenning</surname><given-names>K. R.</given-names></name><name xml:lang="ru"><surname>Бренинг</surname><given-names>К. Р.</given-names></name></name-alternatives><address><country country="RU">Russian Federation</country></address><bio xml:lang="en"><p>Moscow</p></bio><bio xml:lang="ru"><p>Карина Раидовна Бренинг</p><p>Москва</p></bio><email>karina.brening@fccho-moscow.ru</email><xref ref-type="aff" rid="aff1"/></contrib><contrib contrib-type="author"><name-alternatives><name xml:lang="en"><surname>Abramov</surname><given-names>D. S.</given-names></name><name xml:lang="ru"><surname>Абрамов</surname><given-names>Д. С.</given-names></name></name-alternatives><address><country country="RU">Russian Federation</country></address><bio xml:lang="en"><p>Moscow</p></bio><bio xml:lang="ru"><p>Дмитрий Сергеевич Абрамов</p><p>Москва</p></bio><email>abramovd_s@bk.ru</email><xref ref-type="aff" rid="aff1"/></contrib><contrib contrib-type="author"><name-alternatives><name xml:lang="en"><surname>Fominykh</surname><given-names>V. V.</given-names></name><name xml:lang="ru"><surname>Фоминых</surname><given-names>В. В.</given-names></name></name-alternatives><address><country country="RU">Russian Federation</country></address><bio xml:lang="en"><p>Moscow</p></bio><bio xml:lang="ru"><p>Вероника Валерьевна Фоминых</p><p>Москва</p></bio><email>Veronica.Fomynih@fccho-moscow.ru</email><xref ref-type="aff" rid="aff1"/></contrib><contrib contrib-type="author"><name-alternatives><name xml:lang="en"><surname>Senchenko</surname><given-names>M. A.</given-names></name><name xml:lang="ru"><surname>Сенченко</surname><given-names>М. А.</given-names></name></name-alternatives><address><country country="RU">Russian Federation</country></address><bio xml:lang="en"><p>Moscow</p></bio><bio xml:lang="ru"><p>Мария Анатольевна Сенченко</p><p>Москва</p></bio><email>senchenko.mariia@yandex.ru</email><xref ref-type="aff" rid="aff1"/></contrib><contrib contrib-type="author"><name-alternatives><name xml:lang="en"><surname>Chugaeva</surname><given-names>L. Kh.</given-names></name><name xml:lang="ru"><surname>Чугаева</surname><given-names>Л. Х.</given-names></name></name-alternatives><address><country country="RU">Russian Federation</country></address><bio xml:lang="en"><p>Moscow</p></bio><bio xml:lang="ru"><p>Лилия Халитовна Чугаева</p><p>Москва</p></bio><email>anderliliya@gmail.com</email><xref ref-type="aff" rid="aff1"/></contrib><contrib contrib-type="author"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0002-2352-7716</contrib-id><name-alternatives><name xml:lang="en"><surname>Olshanskaya</surname><given-names>Yu. V.</given-names></name><name xml:lang="ru"><surname>Ольшанская</surname><given-names>Ю. В.</given-names></name></name-alternatives><address><country country="RU">Russian Federation</country></address><bio xml:lang="en"><p>Moscow</p></bio><bio xml:lang="ru"><p>Юлия Вячеславовна Ольшанская</p><p>Москва</p></bio><email>yuliya.olshanskaya@fccho-moscow.ru</email><xref ref-type="aff" rid="aff1"/></contrib><contrib contrib-type="author"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0002-2322-5734</contrib-id><name-alternatives><name xml:lang="en"><surname>Novichkova</surname><given-names>G. A.</given-names></name><name xml:lang="ru"><surname>Новичкова</surname><given-names>Г. А.</given-names></name></name-alternatives><address><country country="RU">Russian Federation</country></address><bio xml:lang="en"><p>Moscow</p></bio><bio xml:lang="ru"><p>Галина Анатольевна Новичкова</p><p>Москва</p></bio><email>Galina.Novichkova@fccho-moscow.ru</email><xref ref-type="aff" rid="aff1"/></contrib><contrib contrib-type="author"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0002-4779-1896</contrib-id><name-alternatives><name xml:lang="en"><surname>Myakova</surname><given-names>N. V.</given-names></name><name xml:lang="ru"><surname>Макова</surname><given-names>Н. В.</given-names></name></name-alternatives><address><country country="RU">Russian Federation</country></address><bio xml:lang="en"><p>Moscow</p></bio><bio xml:lang="ru"><p>Наталья Валерьевна Макова</p><p>Москва</p></bio><email>nmiakova@mail.ru</email><xref ref-type="aff" rid="aff1"/></contrib></contrib-group><aff-alternatives id="aff1"><aff><institution xml:lang="en">The Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology of Ministry of Healthсare of the Russian Federation</institution></aff><aff><institution xml:lang="ru">ФГБУ «Национальный медицинский исследовательский центр детской гематологии, онкологии и иммунологии им. Дмитрия Рогачева» Минздрава России</institution></aff></aff-alternatives><aff-alternatives id="aff2"><aff><institution xml:lang="en">Research Institute of Molecular and Cellular Medicine of the Patrice Lumumba Рeoples’ Friendship University of Russia</institution></aff><aff><institution xml:lang="ru">Научно-исследовательский институт молекулярной и клеточной медицины ФГАОУ ВО «Российский университет дружбы народов им. Патриса Лумумбы»</institution></aff></aff-alternatives><pub-date date-type="pub" iso-8601-date="2024-04-19" publication-format="electronic"><day>19</day><month>04</month><year>2024</year></pub-date><volume>23</volume><issue>1</issue><issue-title xml:lang="en"/><issue-title xml:lang="ru"/><fpage>56</fpage><lpage>62</lpage><history><date date-type="received" iso-8601-date="2023-11-15"><day>15</day><month>11</month><year>2023</year></date><date date-type="accepted" iso-8601-date="2024-01-23"><day>23</day><month>01</month><year>2024</year></date></history><permissions><copyright-statement xml:lang="en">Copyright ©; 2024, «D. Rogachev NMRCPHOI»</copyright-statement><copyright-statement xml:lang="ru">Copyright ©; 2024, ФГБУ «НМИЦ ДГОИ им. Дмитрия Рогачева» Минздрава России</copyright-statement><copyright-year>2024</copyright-year><copyright-holder xml:lang="en">«D. Rogachev NMRCPHOI»</copyright-holder><copyright-holder xml:lang="ru">ФГБУ «НМИЦ ДГОИ им. Дмитрия Рогачева» Минздрава России</copyright-holder><ali:free_to_read xmlns:ali="http://www.niso.org/schemas/ali/1.0/"/><license><ali:license_ref xmlns:ali="http://www.niso.org/schemas/ali/1.0/">https://creativecommons.org/licenses/by/4.0</ali:license_ref></license></permissions><self-uri xlink:href="https://hemoncim.com/jour/article/view/780">https://hemoncim.com/jour/article/view/780</self-uri><abstract xml:lang="en"><p>   Burkitt lymphoma (BL) is one of the most common types of non-Hodgkin lymphoma in children. The application of modern risk-adapted treatment regimens has resulted in 85–90 % survival rates in affected patients; however, prognosis still remains poor in case of relapsed/refractory disease. In standard protocols, patients were stratified into risk groups based primarily on disease stage and extent and lactate dehydrogenase levels. Mutations in the TP53 gene are associated with a poor prognosis in many tumors, and lately there have been reports that TP53 status may have prognostic value in pediatric BL. We analyzed therapy outcomes in patients treated in accordance with the B-NHL-2010M protocol according to their TP53 mutational status. We discovered that the 5-year event-free and overall survival rates in the patients with TP53 mutations were 45.3 % and 47.1 % respectively, versus 97.9% and 97.9% in those without TP53 mutations (p &lt; 0.001). Hence, TP53 mutational status is an important prognostic marker in pediatric patients with BL and should be utilized in future protocols. The study was approved by the Independent Ethics Committee and the Scientific Council of the Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology.</p></abstract><trans-abstract xml:lang="ru"><p>   Лимфома Беркитта (ЛБ) – один из наиболее частых типов неходжкинских лимфом детского возраста. При применении современных риск-адаптированных протоколов удается добиться показателей выживаемости 85–90 %, однако в случае рефрактерного течения заболевания или рецидива прогноз остается неблагоприятным. До настоящего времени в стандартных протоколах система стратификации пациентов на группы риска основывалась в основном на стадии заболевания, распространенности опухолевого процесса и уровне лактатдегидрогеназы. Мутации в гене ТР53 ассоциированы с неблагоприятным прогнозом при многих новообразованиях, а в последнее время появились сообщения, что статус ТР53 может иметь прогностическое значение при ЛБ у детей. Мы проанализировали результаты лечения пациентов, получавших терапию по протоколу В-НХЛ-2010М, в зависимости от статуса гена ТР53. Анализ показал, что показатели 5-летней бессобытийной и общей выживаемости пациентов с мутацией в гене TP53 составили 45,3 % и 47,1 % соответственно, а в группе без мутаций – 97,9 % и 97,9 % соответственно (р &lt; 0,001). Таким образом, статус гена ТР53 является важным прогностическим маркером у педиатрических пациентов с ЛБ и должен учитываться в будущих протоколах. Настоящее исследование одобрено независимым этическим комитетом и утверждено решением ученого совета НМИЦ ДГОИ им. Дмитрия Рогачева.</p></trans-abstract><kwd-group xml:lang="en"><kwd>non-Hodgkin lymphomas</kwd><kwd>Burkitt lymphoma</kwd><kwd>children</kwd><kwd>TP53</kwd><kwd>B-NHL-2010M</kwd></kwd-group><kwd-group xml:lang="ru"><kwd>неходжкинские лимфомы</kwd><kwd>лимфома Беркитта</kwd><kwd>дети</kwd><kwd>TP53</kwd><kwd>В-НХЛ-2010М</kwd></kwd-group><funding-group><funding-statement xml:lang="en">Not specified</funding-statement><funding-statement xml:lang="ru">Не указан</funding-statement></funding-group></article-meta></front><body></body><back><ref-list><ref id="B1"><label>1.</label><mixed-citation>Alaggio R., Amador C., Anagnostopoulos I., Attygalle A.D., de Oliveira Araujo I.B., Berti E., et al. The 5<sup>th</sup> edition of the World Health Organization Classification of Haematolymphoid Tumours: Lymphoid Neoplasms. Leukemia 2022; 36 (7): 1720–48. DOI: 10.1038/s41375-022-01620-2</mixed-citation></ref><ref id="B2"><label>2.</label><mixed-citation>Thacker N., Abla O. Epidemiology of Non-Hodgkin Lymphomas in Childhood and Adolescence. In: Abla, O., Attarbaschi, A. (eds) Non-Hodgkin's Lymphoma in Childhood and Adolescence. Springer, Cham; 2019. DOI: 10.1007/978-3-030-11769-6_2.</mixed-citation></ref><ref id="B3"><label>3.</label><mixed-citation>Patte C., Auperin A., Michon J., Behrendt H., Leverger G., Frappaz D., et al. The Société Française d'Oncologie Pédiatrique LMB89 protocol: highly effective multiagent chemotherapy tailored to the tumor burden and initial response in 561 unselected children with B-cell lymphomas and L3 leukemia. Blood 2001; 97 (11): 3370–9. DOI: 10.1182/blood.v97.11.3370</mixed-citation></ref><ref id="B4"><label>4.</label><mixed-citation>Jourdain A., Auperin A., Minard-Colin V., Aladjidi N., Zsiros J., Coze C., et al. Outcome of and prognostic factors for relapse in children and adolescents with mature B-cell lymphoma and leukemia treated in three consecutive prospective “Lymphomes Malins B” protocols. A Société Française des Cancers de l'Enfant study. Haematologica 2015; 100 (6): 810–7. DOI: 10.3324/haematol.2014.121434</mixed-citation></ref><ref id="B5"><label>5.</label><mixed-citation>Woessmann W., Zimmermann M., Meinhardt A., Müller S., Hauch H., Knörr F., et al. Progressive or relapsed Burkitt lymphoma or leukemia in children and adolescents after BFM-type first-line therapy. Blood 2020; 135 (14): 1124–32. DOI: 10.1182/blood.2019003591</mixed-citation></ref><ref id="B6"><label>6.</label><mixed-citation>Samochatova E., Maschan A., Shelikhova L., Myakova N.V., Belogurova M.B., Khlebnikova O.P., et al. Therapy of advanced-stage mature B-cell lymphoma and leukemia in children and adolescents with rituximab and reduced intensity induction chemotherapy (B-NHL 2004M protocol): the results of a multicenterstudy. J Pediatr Hematol Oncol 2014; 36 (5): 395–401. DOI: 10.1097/MPH.0b013e31829d4900</mixed-citation></ref><ref id="B7"><label>7.</label><mixed-citation>Minard-Colin V., Aupérin A., Pillon M., Amos Burke G.A., Barkauskas D.A., Wheatley K., et al. European Intergroup for Childhood Non-Hodgkin Lymphoma; Children’s Oncology Group. Rituximab for High-Risk, Mature B-Cell Non-Hodgkin's Lymphoma in Children. N Engl J Med 2020; 382 (23): 2207–19. DOI: 10.1056/NEJMoa1915315</mixed-citation></ref><ref id="B8"><label>8.</label><mixed-citation>Maschan A., Myakova N., Aleinikova O., Abugova Yu., Ponomareva N., Belogurova M., et al. Rituximab and reduced-intensity chemotherapy in children and adolescents with mature B-cell lymphoma: interim results for 231 patients enrolled in the second Russian–Belorussian multicentre study B-NHL-2010M. Br J Haematol 2019; 186 (3): 477–83. DOI: 10.1111/bjh.15944</mixed-citation></ref><ref id="B9"><label>9.</label><mixed-citation>Love C., Sun Z., Jima D., Li G., Zhang J., Miles R., et al. The genetic landscape of mutations in Burkitt lymphoma. Nat Genet 2012; 44 (12): 1321–5. DOI: 10.1038/ng.2468</mixed-citation></ref><ref id="B10"><label>10.</label><mixed-citation>Olivier M., Hollstein M., Hainaut P. TP53 mutations in human cancers: origins, consequences, and clinical use. Cold Spring Harb Perspect Biol 2010; 2 (1): a001008. DOI: 10.1101/cshperspect.a001008</mixed-citation></ref><ref id="B11"><label>11.</label><mixed-citation>Rowh M., DeMicco A., Horowitz J., Yin B., Yang-Iott K.S., Fusello A.M., et al. Tp53 deletion in B lineage cells predisposes mice to lymphomas with oncogenic translocations. Oncogene 2011; 30 (47): 4757–64. DOI: 10.1038/onc.2011.191</mixed-citation></ref><ref id="B12"><label>12.</label><mixed-citation>Xu-Monette Z., Medeiros L., Li Y., Orlowski R.Z., Andreeff M., Bueso-Ramos C.E., et al. Dysfunction of the TP53 tumor suppressor gene in lymphoid malignancies. Blood 2012; 119 (16): 3668–83. DOI: 10.1182/blood-2011-11-366062</mixed-citation></ref><ref id="B13"><label>13.</label><mixed-citation>Leventaki V., Rodic V., Tripp S., Bayerl M.G., Perkins S.L., Barnette P., et al. TP53 pathway analysis in paediatric Burkitt lymphoma reveals increased MDM4 expression as the only TP53 pathway abnormality detected in a subset of cases. Br J Haematol 2012; 158 (6): 763–71. DOI: 10.1111/j.1365-2141.2012.09243.x</mixed-citation></ref><ref id="B14"><label>14.</label><mixed-citation>Lacy S., Barrans S., Beer P., Painter D., Smith A.G., Roman E., et al. Targeted sequencing in DLBCL, molecular subtypes, and outcomes: a Haematological Malignancy Research Network report. Blood 2020; 135 (20): 1759–71. DOI: 10.1182/blood.2019003535</mixed-citation></ref><ref id="B15"><label>15.</label><mixed-citation>Xu-Monette Z., Wu L., Visco C., Tai Y.C., Tzankov A., Liu W., et al. Mutational profile and prognostic significance of TP53 in diffuse large B-cell lymphoma patients treated with R-CHOP: report from an International DLBCL Rituximab-CHOP Consortium Program Study. Blood 2012; 120 (19): 3986–96. DOI: 10.1182/blood-2012-05-433334</mixed-citation></ref><ref id="B16"><label>16.</label><mixed-citation>Zenz T., Kreuz M., Fuge M., Klapper W., Horn H., Staiger A.M., et al. TP53 mutation and survival in aggressive B cell lymphoma. Int J Cancer 2017; 141 (7): 1381–8. DOI: 10.1002/ijc.30838</mixed-citation></ref><ref id="B17"><label>17.</label><mixed-citation>Newman A., Zaka M., Zhou P., Blain A.E., Erhorn A., Barnard A., et al. Genomic abnormalities of TP53 define distinct risk groups of paediatric B-cell non-Hodgkin lymphoma. Leukemia 2022; 36 (3): 781–9. DOI: 10.1038/s41375-021-01444-6</mixed-citation></ref><ref id="B18"><label>18.</label><mixed-citation>Srinivasan S., Roy Moulik N., Kc A., Narula G., Sankaran H., Prasad M., et al. Increased toxicities in children with Burkitt lymphoma treated with rituximab: experience from a tertiary cancer center in India. Pediatr Blood Cancer 2020; 67 (11): e28682. DOI: 10.1002/pbc.28682</mixed-citation></ref><ref id="B19"><label>19.</label><mixed-citation>Ehrhardt M., Chen Y., Sandlund J., Bluhm E.C., Hayashi R.J., Becktell K., et al. Late health outcomes after contemporary lymphome Malin de Burkitt therapy for mature B-Cell Non-Hodgkin lymphoma: a report from the childhood cancer survivor study. J Clin Oncol: Off J Am Soc Clin Oncol 2019; 37 (28): 2556–70. DOI: 10.1200/JCO.19.00525</mixed-citation></ref><ref id="B20"><label>20.</label><mixed-citation>Attarbaschi A., Carraro E., Ronceray L., Andrés M., Barzilai-Birenboim S., Bomken S., et al. Second malignant neoplasms after treatment of non-Hodgkin’s lymphoma-a retrospective multinational study of 189 children and adolescents. Leukemia 2020; 35 (2): 534–49. DOI: 10.1038/s41375-020-0841-x</mixed-citation></ref><ref id="B21"><label>21.</label><mixed-citation>Panea R., Love C., Shingleton J., Reddy A., Bailey J.A., Moormann A.M., et al. The whole genome landscape of Burkitt lymphoma subtypes. Blood 2019; 134 (19): 1598–607. DOI: 10.1182/blood.2019001880</mixed-citation></ref><ref id="B22"><label>22.</label><mixed-citation>Grande B., Gerhard D., Jiang A., Griner N.B., Abramson J.S., Alexander T.B., et al. Genome-wide discovery of somatic coding and non-coding mutations in pediatric endemic and sporadic Burkitt lymphoma. Blood 2019; 133 (12): 1313–24. DOI: 10.1182/blood-2018-09-871418</mixed-citation></ref><ref id="B23"><label>23.</label><mixed-citation>Griesmann H., Schlereth K., Krause M., Samans B., Stiewe T. p53 and p73 in suppression of Mycdriven lymphomagenesis. Int J Cancer 2009; 124 (2): 502–6. DOI: 10.1002/ijc.23978</mixed-citation></ref><ref id="B24"><label>24.</label><mixed-citation>Yu L., Yu T., Young K. Cross-talk between Myc and p53 in B-cell lymphomas. Chronic Dis Transl Med 2019; 5 (3): 139–54. DOI: 10.1016/j.cdtm.2019.08.001</mixed-citation></ref></ref-list></back></article>
