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Вирус Эпштейна–Барр у детей, больных классической лимфомой Ходжкина
Вирус Эпштейна–Барр у детей, больных классической лимфомой Ходжкина
Ботезату И.В., Валиев Т.Т., Душенькина Т.Е. и др. Вирус Эпштейна–Барр у детей, больных классической лимфомой Ходжкина. Современная Онкология. 2018; 20 (1): 23–28.
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Аннотация
Классическая лимфома Ходжкина (кЛХ) – одно из многочисленных злокачественных новообразований, ассоциированных с вирусом Эпштейна–Барр (ВЭБ). Показано, что ВЭБ-позитивные случаи кЛХ распределяются неравномерно среди всех случаев этого заболевания. На частоту ВЭБ-позитивных случаев кЛХ оказывают влияние демографическая характеристика изучаемой популяции и другие факторы. Россия относится к географическим регионам с низкой заболеваемостью этой формой опухоли. Цель исследования заключалась в изучении гуморального ответа к ВЭБ и уровней вирусной ДНК в плазме крови детей, больных кЛХ, и выяснении значимости обоих маркеров вируса для диагностики и оценки клинических проявлений болезни.
Исследования показали, что уровень инфицированности ВЭБ у детей, больных кЛХ, практически не отличается от такового у здоровых детей, однако активность гуморального ответа оказалась существенно ниже. Изучение состава форменных элементов лейкоцитарного ростка, ответственных за клеточный и гуморальный иммунитет, не позволило объяснить наблюдаемый феномен. В частности, число циркулирующих в крови лейкоцитов у больных до лечения соответствовало нормальным показателям, но оказалось ниже нормальных значений после лечения. И напротив, процентное содержание лимфоцитов у больных до лечения оказалось ниже нормальных значений, но достигло нормальных показателей после лечения. Процентное содержание нейтрофилов и моноцитов у детей до и после лечения практически соответствовало таковым у здоровых лиц. Полученные данные позволяют предположить, что ослабленный гуморальный ответ у детей, больных кЛХ, не связан с измененным составом форменных элементов лейкоцитарного ростка, а обусловлен их сниженной функциональной активностью. Поиск копий ДНК вируса в плазме и смывах полости рта позволил обнаружить их лишь у нескольких больных до проведения терапии и констатировать их полное отсутствие после лечения. Динамическое наблюдение за концентрацией ДНК ВЭБ в плазме крови и гуморальным ответом к ВЭБ у 3 больных показало повышенное содержание числа копий вирусной ДНК до лечения и их снижение до нулевых значений после успешно проведенной терапии. Титры антител при этом оставались на прежнем уровне и не отражали клинического состояния больных. Проведенное исследование позволяет предположить, что повышенная концентрация вирусной ДНК, обнаруженная в плазме больных кЛХ, может стать важным маркером, позволяющим косвенно оценить степень минимальной остаточной болезни и вероятность рецидива заболевания.
Ключевые слова: вирус Эпштейна–Барр, классическая лимфома Ходжкина у детей, гуморальный ответ к ВЭБ, форменные элементы лейкоцитарного ростка (лейкоциты, лимфоциты, нейтрофилы, моноциты), вирусная ДНК в плазме крови больных.
The data obtained have shown that the level of EBV persistence in children with cHL practically does not differ from that in healthy children, however, the activity of the humoral response to EBV was significantly lower. The study of the composition of the elements of the leukocyte germ, responsible for cellular and humoral immunity, did not make it possible to explain the observed phenomenon.
In particular, the number of circulating leukocytes in the patients' blood before the treatment corresponded to normal values, but it turned out to be below the normal values after the treatment. Conversely, the percentage of lymphocytes in patients before treatment turned out to be lower than normal values, but it reached normal values after the treatment. The percentage of neutrophils and monocytes in patients before and after the treatment was almost the same as in healthy individuals. The data obtained suggest that the reduced humoral response in patients with cHL is not associated with the altered composition of the leukocyte germ cells, but due to their reduced functional activity. The search for copies of virus DNA in plasma and oral cavity swabs made it possible to detect them only in some patients before the therapy and to state their complete absence after the treatment. Dynamic observation of the EBV DNA concentration in blood plasma and humoral response to EBV in 3 patients showed increased values viral DNA copies before treatment, and their decrease to zero after successful therapy, while antibody titers remained at the same level and did not reflected the clinical state of patients. It can be assumed that the increased concentration of plasma viral DNA detected in cHD patients can become a marker that allows indirectly estimating the degree of minimal residual disease and the probability of recurrence of the disease.
Key words: Epstein–Barr virus, classical Hodgkin's lymphoma in children, humoral response to EBV, formed elements of leukocyte germ (leukocytes, lymphocytes, neutrophils, monocytes), viral DNA in the blood plasma of patients.
Исследования показали, что уровень инфицированности ВЭБ у детей, больных кЛХ, практически не отличается от такового у здоровых детей, однако активность гуморального ответа оказалась существенно ниже. Изучение состава форменных элементов лейкоцитарного ростка, ответственных за клеточный и гуморальный иммунитет, не позволило объяснить наблюдаемый феномен. В частности, число циркулирующих в крови лейкоцитов у больных до лечения соответствовало нормальным показателям, но оказалось ниже нормальных значений после лечения. И напротив, процентное содержание лимфоцитов у больных до лечения оказалось ниже нормальных значений, но достигло нормальных показателей после лечения. Процентное содержание нейтрофилов и моноцитов у детей до и после лечения практически соответствовало таковым у здоровых лиц. Полученные данные позволяют предположить, что ослабленный гуморальный ответ у детей, больных кЛХ, не связан с измененным составом форменных элементов лейкоцитарного ростка, а обусловлен их сниженной функциональной активностью. Поиск копий ДНК вируса в плазме и смывах полости рта позволил обнаружить их лишь у нескольких больных до проведения терапии и констатировать их полное отсутствие после лечения. Динамическое наблюдение за концентрацией ДНК ВЭБ в плазме крови и гуморальным ответом к ВЭБ у 3 больных показало повышенное содержание числа копий вирусной ДНК до лечения и их снижение до нулевых значений после успешно проведенной терапии. Титры антител при этом оставались на прежнем уровне и не отражали клинического состояния больных. Проведенное исследование позволяет предположить, что повышенная концентрация вирусной ДНК, обнаруженная в плазме больных кЛХ, может стать важным маркером, позволяющим косвенно оценить степень минимальной остаточной болезни и вероятность рецидива заболевания.
Ключевые слова: вирус Эпштейна–Барр, классическая лимфома Ходжкина у детей, гуморальный ответ к ВЭБ, форменные элементы лейкоцитарного ростка (лейкоциты, лимфоциты, нейтрофилы, моноциты), вирусная ДНК в плазме крови больных.
________________________________________________
The data obtained have shown that the level of EBV persistence in children with cHL practically does not differ from that in healthy children, however, the activity of the humoral response to EBV was significantly lower. The study of the composition of the elements of the leukocyte germ, responsible for cellular and humoral immunity, did not make it possible to explain the observed phenomenon.
In particular, the number of circulating leukocytes in the patients' blood before the treatment corresponded to normal values, but it turned out to be below the normal values after the treatment. Conversely, the percentage of lymphocytes in patients before treatment turned out to be lower than normal values, but it reached normal values after the treatment. The percentage of neutrophils and monocytes in patients before and after the treatment was almost the same as in healthy individuals. The data obtained suggest that the reduced humoral response in patients with cHL is not associated with the altered composition of the leukocyte germ cells, but due to their reduced functional activity. The search for copies of virus DNA in plasma and oral cavity swabs made it possible to detect them only in some patients before the therapy and to state their complete absence after the treatment. Dynamic observation of the EBV DNA concentration in blood plasma and humoral response to EBV in 3 patients showed increased values viral DNA copies before treatment, and their decrease to zero after successful therapy, while antibody titers remained at the same level and did not reflected the clinical state of patients. It can be assumed that the increased concentration of plasma viral DNA detected in cHD patients can become a marker that allows indirectly estimating the degree of minimal residual disease and the probability of recurrence of the disease.
Key words: Epstein–Barr virus, classical Hodgkin's lymphoma in children, humoral response to EBV, formed elements of leukocyte germ (leukocytes, lymphocytes, neutrophils, monocytes), viral DNA in the blood plasma of patients.
Полный текст
Список литературы
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13. Anderson LJ, Longnecker R. Epstein-Barr virus latent membrane protein 2A exploits Notch1 to alter B-cell identity in vivo. Blood 2009; 113: 108–16.
14. Soni V, Cahir-McFarland E, Kieff E. LMP1 TRAFficking activates growth and survival pathways. Adv Exp Med Biol 2007; 597: 173–87.
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16. Wang F, Gregory C, Sample C et al. Epstein-Barr virus latent membrane protein (LMP1) and nuclear proteins 2 and 3C are effectors of phenotypic changes in B lymphocytes: EBNA-2 and LMP1 cooperatively induce CD23. J Virol 1990; 64: 2309–18.
17. Henderson S, Rowe M, Gregory C et al. Induction of bcl-2 expression by Epstein-Barr virus latent membrane protein 1 protects infected B cells from programmed cell death. Cell 1991; 65: 1107–15.
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26. Diepstra A, Niens M, Vellenga E et al. Association with HLA class I in Epstein-Barr-virus-positive and with HLA class III in Epstein-Barr-virus-negative Hodgkin's lymphoma. Lancet 2005; 365: 2216–24.
27. Huang X, Kushekhar K, Nolte I et al. HLA associations in classical Hodgkin lymphoma: EBV status matters. PLoS One 2012; 7: e39986.
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29. Urayama KY, Jarrett RF, Hjalgrim H et al. Genome-wide association study of classical Hodgkin lymphoma and Epstein-Barr virus status-defined subgroups. J Natl Cancer Inst 2012; 104: 240–53.
30. Glaser SL, Lin RJ, Stewart SL et al. Epstein-Barr virus-associated Hodgkin's disease: epidemiologic characteristics in international data. Int J Cancer 1997; 70: 375–82.
31. Jarrett AF, Armstrong AA, Alexander E. Epidemiology of EBV and Hodgkin's lymphoma. Ann Oncol 1996; 7 (4): 5–10.
32. Jarrett RF, Gallagher A, Jones DB et al. Detection of Epstein-Barr virus genomes in Hodgkin's disease: relation to age. J Clin Pathol 1991; 44: 844–8.
33. Детская онкология. Национальное руководство. Под ред. М.Д.Алиева, В.Г.Полякова, Г.Л.Менткевича, С.А.Маяковой. М.: Издательская группа РОНЦ, 2012. / Detskaia onkologiia. Natsional'noe rukovodstvo. Pod red. M.D.Alieva, V.G.Poliakova, G.L.Mentkevicha, S.A.Maiakovoi. M.: Izdatel'skaia gruppa RONTs, 2012. [in Russian]
34. Stein H, Delsol G, Pileri SA et al. Classical Hodgkin lymphoma, introduction. In: Swerdlow SH, Campo E, Harris NL et al (eds) WHO classification of tumours of haematopoietic and lymphoid tissues. IARC, Lyon, 2008.
35. Botezatu IV, Kondratova VN, Shelepov VP et al. DNA melting analysis: application of the "open tube" format for detection of mutant KRAS. Anal Biochem 2011; 419: 302–8.
36. Gallagher A, Perry J, Freeland J et al. Hodgkin lymphoma and Epstein-Barr virus (EBV): no evidence to support hit-and-run mechanism in cases classified as non-EBV-associated. Int J Cancer 2003; 104: 624–30.
2. Abbott RJ, Pachnio A, Pedroza-Pacheco I et al. Asymptomatic Primary Infection with Epstein-Barr Virus: Observations on Young Adult Cases. J Virol 2017; 91 (21): e00382–17.
3. Kang MS, Kieff E. Epstein-Barr virus latent genes. Exp Mol Med 2015; 47 (1): e131.
4. Gallo A, Vella S, Miele M et al. Global profiling of viral and cellular non-coding RNAs in Epstein-Barr virus-induced lymphoblastoid cell lines and released exosome cargos. Cancer Lett 2017; 388: 334–43.
5. Piedade D, Azevedo-Pereira JM. The Role of microRNAs in the Pathogenesis of Herpesvirus Infection. Viruses 2016; 8 (6). pii: E156. DOI: 10.3390/v8060156
6. Young LS, Murray PG. Epstein-Barr virus and oncogenesis: from latent genes to tumours. Oncogene 2003; 22: 5108–21.
7. Alexander FE, Jarrett RF, Lawrence D et al. Risk factors for Hodgkin's disease by Epstein-Barr virus (EBV) status: prior infection by EBV and other. Br J Cancer 2000; 82:1117–21.
8. Mueller N, Evans A, Harris NL et al. Hodgkin's disease and Epstein-Barr virus. Altered antibody pattern before diagnosis. N Engl J Med 1989; 320: 689–95.
9. Anagnostopoulos I, Herbst H, Niedobitek G et al. Demonstration of monoclonal EBV genomes in Hodgkin's disease and Ki-1-positive anaplastic large cell lymphoma by combined Southern blot and in situ hybridization. Blood 1989; 74: 810–6.
10. Tanyildiz HG, Yildiz I, Bassullu N et al. The Role of Epstein-Barr Virus LMP-1 Immunohistochemical Staining in Childhood Hodgkin Lymphoma. Iran J Pediatr 2015; 25: e2359.
11. Iwakiri D, Takada K. Role of EBERs in the pathogenesis of EBV infection. Adv Cancer Res 2010; 107: 119–36.
12. Vockerodt M, Wei W, Nagy E et al. Suppression of the LMP2A target gene, EGR-1, protects Hodgkin's lymphoma cells from entry to the EBV lytic cycle. J Pathol 2013; 230: 399–409.
13. Anderson LJ, Longnecker R. Epstein-Barr virus latent membrane protein 2A exploits Notch1 to alter B-cell identity in vivo. Blood 2009; 113: 108–16.
14. Soni V, Cahir-McFarland E, Kieff E. LMP1 TRAFficking activates growth and survival pathways. Adv Exp Med Biol 2007; 597: 173–87.
15. Eliopoulos AG, Young LS. LMP1 structure and signal transduction. Semin Cancer Biol 2001; 11: 435–44.
16. Wang F, Gregory C, Sample C et al. Epstein-Barr virus latent membrane protein (LMP1) and nuclear proteins 2 and 3C are effectors of phenotypic changes in B lymphocytes: EBNA-2 and LMP1 cooperatively induce CD23. J Virol 1990; 64: 2309–18.
17. Henderson S, Rowe M, Gregory C et al. Induction of bcl-2 expression by Epstein-Barr virus latent membrane protein 1 protects infected B cells from programmed cell death. Cell 1991; 65: 1107–15.
18. Laherty CD, Hu HM, Opipari AW et al. The Epstein-Barr virus LMP1 gene product induces A20 zinc finger protein expression by activating nuclear factor kappa B. J Biol Chem 1992; 267: 24157–60.
19. Uchida J, Yasui T, Takaoka-Shichijo Y et al. Mimicry of CD40 signals by Epstein-Barr virus LMP1 in B lymphocyte responses. Science 1999; 286: 300–3.
20. Schwarzer R, Dorken B, Jundt F. Notch is an essential upstream regulator of NF-kappaB and is relevant for survival of Hodgkin and Reed-Sternberg cells. Leukemia 2012; 26: 806–13.
21. Khan G, Miyashita EM, Yang B et al. Is EBV persistence in vivo a model for B cell homeostasis? Immunity 1996; 5: 173–9.
22. Alexander FE, McKinney PA, Williams J et al. Epidemiological evidence for the 'two-disease hypothesis' in Hodgkin's disease. Int J Epidemiol 1991; 20: 354–61.
23. Levin LI, Chang ET, Ambinder RF et al. Atypical prediagnosis Epstein-Barr virus serology restricted to EBV-positive Hodgkin lymphoma. Blood 2012; 120: 3750–5.
24. Henle W, Henle G, Andersson J et al. Antibody responses to Epstein-Barr virus-determined nuclear antigen (EBNA)-1 and EBNA-2 in acute and chronic Epstein-Barr virus infection. Proc Natl Acad Sci U. S. A 1987; 84: 570–4.
25. Chang ET, Zheng T, Lennette ET et al. Heterogeneity of risk factors and antibody profiles in epstein-barr virus genome-positive and -negative hodgkin lymphoma. J Infect Dis 2004; 189: 2271–81.
26. Diepstra A, Niens M, Vellenga E et al. Association with HLA class I in Epstein-Barr-virus-positive and with HLA class III in Epstein-Barr-virus-negative Hodgkin's lymphoma. Lancet 2005; 365: 2216–24.
27. Huang X, Kushekhar K, Nolte I et al. HLA associations in classical Hodgkin lymphoma: EBV status matters. PLoS One 2012; 7: e39986.
28. Niens M, Jarrett RF, Hepkema B et al. HLA-A*02 is associated with a reduced risk and HLA-A*01 with an increased risk of developing EBV+ Hodgkin lymphoma. Blood 2007; 110: 3310–5.
29. Urayama KY, Jarrett RF, Hjalgrim H et al. Genome-wide association study of classical Hodgkin lymphoma and Epstein-Barr virus status-defined subgroups. J Natl Cancer Inst 2012; 104: 240–53.
30. Glaser SL, Lin RJ, Stewart SL et al. Epstein-Barr virus-associated Hodgkin's disease: epidemiologic characteristics in international data. Int J Cancer 1997; 70: 375–82.
31. Jarrett AF, Armstrong AA, Alexander E. Epidemiology of EBV and Hodgkin's lymphoma. Ann Oncol 1996; 7 (4): 5–10.
32. Jarrett RF, Gallagher A, Jones DB et al. Detection of Epstein-Barr virus genomes in Hodgkin's disease: relation to age. J Clin Pathol 1991; 44: 844–8.
33. Detskaia onkologiia. Natsional'noe rukovodstvo. Pod red. M.D.Alieva, V.G.Poliakova, G.L.Mentkevicha, S.A.Maiakovoi. M.: Izdatel'skaia gruppa RONTs, 2012. [in Russian]
34. Stein H, Delsol G, Pileri SA et al. Classical Hodgkin lymphoma, introduction. In: Swerdlow SH, Campo E, Harris NL et al (eds) WHO classification of tumours of haematopoietic and lymphoid tissues. IARC, Lyon, 2008.
35. Botezatu IV, Kondratova VN, Shelepov VP et al. DNA melting analysis: application of the "open tube" format for detection of mutant KRAS. Anal Biochem 2011; 419: 302–8.
36. Gallagher A, Perry J, Freeland J et al. Hodgkin lymphoma and Epstein-Barr virus (EBV): no evidence to support hit-and-run mechanism in cases classified as non-EBV-associated. Int J Cancer 2003; 104: 624–30.
2. Abbott RJ, Pachnio A, Pedroza-Pacheco I et al. Asymptomatic Primary Infection with Epstein-Barr Virus: Observations on Young Adult Cases. J Virol 2017; 91 (21): e00382–17.
3. Kang MS, Kieff E. Epstein-Barr virus latent genes. Exp Mol Med 2015; 47 (1): e131.
4. Gallo A, Vella S, Miele M et al. Global profiling of viral and cellular non-coding RNAs in Epstein-Barr virus-induced lymphoblastoid cell lines and released exosome cargos. Cancer Lett 2017; 388: 334–43.
5. Piedade D, Azevedo-Pereira JM. The Role of microRNAs in the Pathogenesis of Herpesvirus Infection. Viruses 2016; 8 (6). pii: E156. DOI: 10.3390/v8060156
6. Young LS, Murray PG. Epstein-Barr virus and oncogenesis: from latent genes to tumours. Oncogene 2003; 22: 5108–21.
7. Alexander FE, Jarrett RF, Lawrence D et al. Risk factors for Hodgkin's disease by Epstein-Barr virus (EBV) status: prior infection by EBV and other. Br J Cancer 2000; 82:1117–21.
8. Mueller N, Evans A, Harris NL et al. Hodgkin's disease and Epstein-Barr virus. Altered antibody pattern before diagnosis. N Engl J Med 1989; 320: 689–95.
9. Anagnostopoulos I, Herbst H, Niedobitek G et al. Demonstration of monoclonal EBV genomes in Hodgkin's disease and Ki-1-positive anaplastic large cell lymphoma by combined Southern blot and in situ hybridization. Blood 1989; 74: 810–6.
10. Tanyildiz HG, Yildiz I, Bassullu N et al. The Role of Epstein-Barr Virus LMP-1 Immunohistochemical Staining in Childhood Hodgkin Lymphoma. Iran J Pediatr 2015; 25: e2359.
11. Iwakiri D, Takada K. Role of EBERs in the pathogenesis of EBV infection. Adv Cancer Res 2010; 107: 119–36.
12. Vockerodt M, Wei W, Nagy E et al. Suppression of the LMP2A target gene, EGR-1, protects Hodgkin's lymphoma cells from entry to the EBV lytic cycle. J Pathol 2013; 230: 399–409.
13. Anderson LJ, Longnecker R. Epstein-Barr virus latent membrane protein 2A exploits Notch1 to alter B-cell identity in vivo. Blood 2009; 113: 108–16.
14. Soni V, Cahir-McFarland E, Kieff E. LMP1 TRAFficking activates growth and survival pathways. Adv Exp Med Biol 2007; 597: 173–87.
15. Eliopoulos AG, Young LS. LMP1 structure and signal transduction. Semin Cancer Biol 2001; 11: 435–44.
16. Wang F, Gregory C, Sample C et al. Epstein-Barr virus latent membrane protein (LMP1) and nuclear proteins 2 and 3C are effectors of phenotypic changes in B lymphocytes: EBNA-2 and LMP1 cooperatively induce CD23. J Virol 1990; 64: 2309–18.
17. Henderson S, Rowe M, Gregory C et al. Induction of bcl-2 expression by Epstein-Barr virus latent membrane protein 1 protects infected B cells from programmed cell death. Cell 1991; 65: 1107–15.
18. Laherty CD, Hu HM, Opipari AW et al. The Epstein-Barr virus LMP1 gene product induces A20 zinc finger protein expression by activating nuclear factor kappa B. J Biol Chem 1992; 267: 24157–60.
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20. Schwarzer R, Dorken B, Jundt F. Notch is an essential upstream regulator of NF-kappaB and is relevant for survival of Hodgkin and Reed-Sternberg cells. Leukemia 2012; 26: 806–13.
21. Khan G, Miyashita EM, Yang B et al. Is EBV persistence in vivo a model for B cell homeostasis? Immunity 1996; 5: 173–9.
22. Alexander FE, McKinney PA, Williams J et al. Epidemiological evidence for the 'two-disease hypothesis' in Hodgkin's disease. Int J Epidemiol 1991; 20: 354–61.
23. Levin LI, Chang ET, Ambinder RF et al. Atypical prediagnosis Epstein-Barr virus serology restricted to EBV-positive Hodgkin lymphoma. Blood 2012; 120: 3750–5.
24. Henle W, Henle G, Andersson J et al. Antibody responses to Epstein-Barr virus-determined nuclear antigen (EBNA)-1 and EBNA-2 in acute and chronic Epstein-Barr virus infection. Proc Natl Acad Sci U. S. A 1987; 84: 570–4.
25. Chang ET, Zheng T, Lennette ET et al. Heterogeneity of risk factors and antibody profiles in epstein-barr virus genome-positive and -negative hodgkin lymphoma. J Infect Dis 2004; 189: 2271–81.
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27. Huang X, Kushekhar K, Nolte I et al. HLA associations in classical Hodgkin lymphoma: EBV status matters. PLoS One 2012; 7: e39986.
28. Niens M, Jarrett RF, Hepkema B et al. HLA-A*02 is associated with a reduced risk and HLA-A*01 with an increased risk of developing EBV+ Hodgkin lymphoma. Blood 2007; 110: 3310–5.
29. Urayama KY, Jarrett RF, Hjalgrim H et al. Genome-wide association study of classical Hodgkin lymphoma and Epstein-Barr virus status-defined subgroups. J Natl Cancer Inst 2012; 104: 240–53.
30. Glaser SL, Lin RJ, Stewart SL et al. Epstein-Barr virus-associated Hodgkin's disease: epidemiologic characteristics in international data. Int J Cancer 1997; 70: 375–82.
31. Jarrett AF, Armstrong AA, Alexander E. Epidemiology of EBV and Hodgkin's lymphoma. Ann Oncol 1996; 7 (4): 5–10.
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34. Stein H, Delsol G, Pileri SA et al. Classical Hodgkin lymphoma, introduction. In: Swerdlow SH, Campo E, Harris NL et al (eds) WHO classification of tumours of haematopoietic and lymphoid tissues. IARC, Lyon, 2008.
35. Botezatu IV, Kondratova VN, Shelepov VP et al. DNA melting analysis: application of the "open tube" format for detection of mutant KRAS. Anal Biochem 2011; 419: 302–8.
36. Gallagher A, Perry J, Freeland J et al. Hodgkin lymphoma and Epstein-Barr virus (EBV): no evidence to support hit-and-run mechanism in cases classified as non-EBV-associated. Int J Cancer 2003; 104: 624–30.
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16. Wang F, Gregory C, Sample C et al. Epstein-Barr virus latent membrane protein (LMP1) and nuclear proteins 2 and 3C are effectors of phenotypic changes in B lymphocytes: EBNA-2 and LMP1 cooperatively induce CD23. J Virol 1990; 64: 2309–18.
17. Henderson S, Rowe M, Gregory C et al. Induction of bcl-2 expression by Epstein-Barr virus latent membrane protein 1 protects infected B cells from programmed cell death. Cell 1991; 65: 1107–15.
18. Laherty CD, Hu HM, Opipari AW et al. The Epstein-Barr virus LMP1 gene product induces A20 zinc finger protein expression by activating nuclear factor kappa B. J Biol Chem 1992; 267: 24157–60.
19. Uchida J, Yasui T, Takaoka-Shichijo Y et al. Mimicry of CD40 signals by Epstein-Barr virus LMP1 in B lymphocyte responses. Science 1999; 286: 300–3.
20. Schwarzer R, Dorken B, Jundt F. Notch is an essential upstream regulator of NF-kappaB and is relevant for survival of Hodgkin and Reed-Sternberg cells. Leukemia 2012; 26: 806–13.
21. Khan G, Miyashita EM, Yang B et al. Is EBV persistence in vivo a model for B cell homeostasis? Immunity 1996; 5: 173–9.
22. Alexander FE, McKinney PA, Williams J et al. Epidemiological evidence for the 'two-disease hypothesis' in Hodgkin's disease. Int J Epidemiol 1991; 20: 354–61.
23. Levin LI, Chang ET, Ambinder RF et al. Atypical prediagnosis Epstein-Barr virus serology restricted to EBV-positive Hodgkin lymphoma. Blood 2012; 120: 3750–5.
24. Henle W, Henle G, Andersson J et al. Antibody responses to Epstein-Barr virus-determined nuclear antigen (EBNA)-1 and EBNA-2 in acute and chronic Epstein-Barr virus infection. Proc Natl Acad Sci U. S. A 1987; 84: 570–4.
25. Chang ET, Zheng T, Lennette ET et al. Heterogeneity of risk factors and antibody profiles in epstein-barr virus genome-positive and -negative hodgkin lymphoma. J Infect Dis 2004; 189: 2271–81.
26. Diepstra A, Niens M, Vellenga E et al. Association with HLA class I in Epstein-Barr-virus-positive and with HLA class III in Epstein-Barr-virus-negative Hodgkin's lymphoma. Lancet 2005; 365: 2216–24.
27. Huang X, Kushekhar K, Nolte I et al. HLA associations in classical Hodgkin lymphoma: EBV status matters. PLoS One 2012; 7: e39986.
28. Niens M, Jarrett RF, Hepkema B et al. HLA-A*02 is associated with a reduced risk and HLA-A*01 with an increased risk of developing EBV+ Hodgkin lymphoma. Blood 2007; 110: 3310–5.
29. Urayama KY, Jarrett RF, Hjalgrim H et al. Genome-wide association study of classical Hodgkin lymphoma and Epstein-Barr virus status-defined subgroups. J Natl Cancer Inst 2012; 104: 240–53.
30. Glaser SL, Lin RJ, Stewart SL et al. Epstein-Barr virus-associated Hodgkin's disease: epidemiologic characteristics in international data. Int J Cancer 1997; 70: 375–82.
31. Jarrett AF, Armstrong AA, Alexander E. Epidemiology of EBV and Hodgkin's lymphoma. Ann Oncol 1996; 7 (4): 5–10.
32. Jarrett RF, Gallagher A, Jones DB et al. Detection of Epstein-Barr virus genomes in Hodgkin's disease: relation to age. J Clin Pathol 1991; 44: 844–8.
33. Detskaia onkologiia. Natsional'noe rukovodstvo. Pod red. M.D.Alieva, V.G.Poliakova, G.L.Mentkevicha, S.A.Maiakovoi. M.: Izdatel'skaia gruppa RONTs, 2012. [in Russian]
34. Stein H, Delsol G, Pileri SA et al. Classical Hodgkin lymphoma, introduction. In: Swerdlow SH, Campo E, Harris NL et al (eds) WHO classification of tumours of haematopoietic and lymphoid tissues. IARC, Lyon, 2008.
35. Botezatu IV, Kondratova VN, Shelepov VP et al. DNA melting analysis: application of the "open tube" format for detection of mutant KRAS. Anal Biochem 2011; 419: 302–8.
36. Gallagher A, Perry J, Freeland J et al. Hodgkin lymphoma and Epstein-Barr virus (EBV): no evidence to support hit-and-run mechanism in cases classified as non-EBV-associated. Int J Cancer 2003; 104: 624–30.
Авторы
И.В.Ботезату, Т.Т.Валиев, Т.Е.Душенькина, К.В.Смирнова, Р.С.Равшанова, Д.М.Максимович, А.В.Лихтенштейн, В.Э.Гурцевич*, А.В.Попа, Н.Б.Сенюта
ФГБУ «Национальный медицинский исследовательский центр онкологии им. Н.Н.Блохина» Минздрава России. 115478, Россия, Москва, Каширское ш., д. 23
*vlad-88@yandex.ru
N.N.Blokhin National Medical Research Center of Oncology of the Ministry of Health of the Russian Federation. 115478, Russian Federation, Moscow, Kashirskoe sh., d. 23
*vlad-88@yandex.ru
ФГБУ «Национальный медицинский исследовательский центр онкологии им. Н.Н.Блохина» Минздрава России. 115478, Россия, Москва, Каширское ш., д. 23
*vlad-88@yandex.ru
________________________________________________
N.N.Blokhin National Medical Research Center of Oncology of the Ministry of Health of the Russian Federation. 115478, Russian Federation, Moscow, Kashirskoe sh., d. 23
*vlad-88@yandex.ru
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