Структура и значение цитогенетических перестроек у взрослых больных Ph-негативным острым лимфобластным лейкозом - Журнал Терапевтический архив № 7 Вопросы гематологии 2018
Структура и значение цитогенетических перестроек у взрослых больных Ph-негативным острым лимфобластным лейкозом
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Аннотация
Цель исследования. Определить частоту, спектр, структурные особенности и прогностическое значение цитогенетических нарушений у взрослых больных Ph-негативным острым лимфобластным лейкозом (ОЛЛ) на терапии по протоколу ОЛЛ-2009.
Материалы и методы. В исследование включено 115 взрослых пациентов с впервые выявленным Ph-негативным ОЛЛ: 58 мужчин и 57 женщин в возрасте от 15 до 61 года (средний возраст 26,5 лет), которые проходили лечение с июня 2009 по сентябрь 2016 г. в ФГБУ «НМИЦ гематологии» МЗ РФ (n=101) и в гематологических отделениях областных клинических больниц (n=14). Всем пациентам проводили терапию по протоколу ОЛЛ-2009 (ClinicalTrials.gov, NCT01193933). Медиана наблюдения составила 24,5 мес (0,2–94,4 мес). В ходе исследования были проанализированы результаты стандартного цитогенетического исследования (СЦИ), и на архивном биологическом материале всем пациентам выполнена флуоресцентная гибридизация in situ (FISH) с использованием ДНК-зондов для выявления структурных перестроек в локусах генов MLL/t(11q23), с-MYC/t(8q24), TP53/делеция 17p13, CDKN2A/делеция 9p21, транслокаций t(1;19)/E2A-PBX1 и t(12;21)/ETV6-RUNX1; iAMP21.
Результаты. При СЦИ кариотип определен у 86% больных. Из них нормальный кариотип выявлен у 48,5%, хромосомные аберрации – у 51,5% (структурные перестройки выявлены у 19,2%, гиперплоидия у 27,2%, гипоплоидия у 5,1%). У 17,2% пациентов установлены комплексные нарушения кариотипа. При FISH-исследовании аберрации выявлены у 67% больных: делеция 9p21/CDKN2A у 24,3%, перестройки гена MLL/t(11q23) у 7,8%, делеция 17p13/TP53 у 5,2%, перестройки гена c-MYC/t(8q24) у 1,7%, t(1;19)/E2A-PBX1 у 0,8%, iAMP21 у 0,8% больных, другие нарушения (дополнительные сигналы/отсутствие сигналов от локусов генов) у 26,4%, t(12;21)/ETV6-RUNX1 не выявлена. Применение метода FISH в дополнение к СЦИ позволяет увеличить частоту выявления аберрантного кариотипа с 51,5 до 67%. Показана статистически значимая корреляция делеции 9p21/CDKN2A с высокой активностью лактатдегидрогеназы в крови (p=0,02); перестроек гена MLL/t(11q23) – с лейкоцитозом и высоким содержанием бластных клеток в крови (p=0,0016), гиперплоидии – с нормальным количеством лейкоцитов в крови (p=0,02). В группах с различными цитогенетическими нарушениями не выявлено статистически значимых различий в эффективности лечения по протоколу ОЛЛ-2009 (в сроках достижения полной ремиссии, ранней летальности и резистентности). При анализе связи цитогенетических нарушений и их сочетаний с долгосрочными результатами по протоколу ОЛЛ-2009 статистически значимое влияние на безрецидивную выживаемость (относительный риск – HR – 176,9; p<0,0001) и вероятность развития рецидива (HR – 6,4; p=0,02) оказали только два признака – наличие перестроек генов MLL/t(11q23) и c-MYC/t(8q24).
Заключение. Неблагоприятными прогностическими факторами в рамках терапевтического воздействия, предусмотренного протоколом ОЛЛ-2009, являются перестройки генов MLL/t(11q23) и с-MYC/t(8q24). Делеции генов CDKN2A/9p21 и TP53/17p13, численные и комплексные нарушения кариотипа не являются факторами прогноза у взрослых больных Ph-негативным ОЛЛ при использовании протокола ОЛЛ-2009.
Ключевые слова: Ph-негативный острый лимфобластный лейкоз, хромосомные аберрации, протокол ОЛЛ-2009, факторы риска, флуоресцентная гибридизация in situ.
Materials and methods. The study included 115 adult patients with firstly diagnosed Ph-negative ALL: 58 male and 57 female aged from 15 to 61 years (mean age 26.5 years), who underwent treatment from September 2009 to September 2015 in National Medical Research Center for Hematology MH RF (n=101) and in hematology departments of regional hospitals (n=14). All patients received therapy of ALL-2009 protocol (ClinicalTrials.gov, NCT01193933). The median follow-up was 24.5 months (0.2-94.4 months). As a part of the study results of a standard cytogenetic assay (SCA) were analyzed and fluorescence hybridization in situ (FISH) with the use of DNA-probes was performed on archived biological material for structural changes in gene locuses MLL/t(11q23), с-MYC/t(8q24), TP53/ deletion 17p13, CDKN2A/ deletion 9p21, translocation t(1;19)/E2A-PBX1 и t(12;21)/ETV6-RUNX1; iAMP21 identification.
Results. Karyotype was defined using SCA in 86% of patients. Normal karyotype was found in 48.5% of them, chromosome aberrations in 51.5% (structural changes were found in 19.2%, hyperploidy in 27.2%, and hypoploidy in 5.1%). In 17.2% of patients complex karyotype abnormalities were found. With the use of FISH technique aberrations were found in 67% of patients: 9p21/CDKN2A deletion in 24.3%, MLL/t(11q23) gene abnormalities in 7.8%, 17p13/TP53 deletion in 5.2%, abnormalities of c-MYC/t(8q24) in 1.7%, t(1;19)/E2A-PBX1 in 0.8%, and iAMP21 in 0.8%, other abnormalities (additional signals/absence of signals from gene locuses) in 26.4%, t(12;21)/ETV6-RUNX1 was not found. FISH technique use in addition to SCA allows to increase aberrant karyotype location from 51.5 to 67%. A statistically significant correlation of 9p21/CDKN2A deletion with high serum lactate dehydrogenase activity (p=0.02); MLL/t(11q23) gene abnormalities – with leucocytosis and high blast cells level in blood (p=0.0016), hyperploidy – with normal leukocyte count (p=0.02) was shown. In groups with different cytogenetic abnormalities no statistically significant differences of treatment with ALL-2009 protocol were found (in terms of complete remission, early mortality and treatment resistance). When connection of cytogenetic abnormalities and their combinations with long-term results were analyzed according to ALL-2009 protocol, only two characteristics – MLL/t(11q23) and c-MYC/t(8q24) gene abnormalities had a statistically significant influence on disease-free survival (HR – 176.9; p<0.0001) and chance of recurrence (HR – 6.4; p=0.02)
Conclusion. Adverse prognostic factors in terms of therapeutic management provided in ALL-2009 protocol were MLL/t(11q23) and с-MYC/t(8q24) genes abnormalities. CDKN2A/9p21 and TP53/17p13 genes deletions, quantative and complex karyotype abnormalities were not prognostic factors in adult patients with Ph-negative ALL in ALL-2009 protocol use.
Keywords: Ph-negative acute lymphoblastic leukemia, chromosome aberrations, ALL-2009 protocol, risk factors, FISH.
Материалы и методы. В исследование включено 115 взрослых пациентов с впервые выявленным Ph-негативным ОЛЛ: 58 мужчин и 57 женщин в возрасте от 15 до 61 года (средний возраст 26,5 лет), которые проходили лечение с июня 2009 по сентябрь 2016 г. в ФГБУ «НМИЦ гематологии» МЗ РФ (n=101) и в гематологических отделениях областных клинических больниц (n=14). Всем пациентам проводили терапию по протоколу ОЛЛ-2009 (ClinicalTrials.gov, NCT01193933). Медиана наблюдения составила 24,5 мес (0,2–94,4 мес). В ходе исследования были проанализированы результаты стандартного цитогенетического исследования (СЦИ), и на архивном биологическом материале всем пациентам выполнена флуоресцентная гибридизация in situ (FISH) с использованием ДНК-зондов для выявления структурных перестроек в локусах генов MLL/t(11q23), с-MYC/t(8q24), TP53/делеция 17p13, CDKN2A/делеция 9p21, транслокаций t(1;19)/E2A-PBX1 и t(12;21)/ETV6-RUNX1; iAMP21.
Результаты. При СЦИ кариотип определен у 86% больных. Из них нормальный кариотип выявлен у 48,5%, хромосомные аберрации – у 51,5% (структурные перестройки выявлены у 19,2%, гиперплоидия у 27,2%, гипоплоидия у 5,1%). У 17,2% пациентов установлены комплексные нарушения кариотипа. При FISH-исследовании аберрации выявлены у 67% больных: делеция 9p21/CDKN2A у 24,3%, перестройки гена MLL/t(11q23) у 7,8%, делеция 17p13/TP53 у 5,2%, перестройки гена c-MYC/t(8q24) у 1,7%, t(1;19)/E2A-PBX1 у 0,8%, iAMP21 у 0,8% больных, другие нарушения (дополнительные сигналы/отсутствие сигналов от локусов генов) у 26,4%, t(12;21)/ETV6-RUNX1 не выявлена. Применение метода FISH в дополнение к СЦИ позволяет увеличить частоту выявления аберрантного кариотипа с 51,5 до 67%. Показана статистически значимая корреляция делеции 9p21/CDKN2A с высокой активностью лактатдегидрогеназы в крови (p=0,02); перестроек гена MLL/t(11q23) – с лейкоцитозом и высоким содержанием бластных клеток в крови (p=0,0016), гиперплоидии – с нормальным количеством лейкоцитов в крови (p=0,02). В группах с различными цитогенетическими нарушениями не выявлено статистически значимых различий в эффективности лечения по протоколу ОЛЛ-2009 (в сроках достижения полной ремиссии, ранней летальности и резистентности). При анализе связи цитогенетических нарушений и их сочетаний с долгосрочными результатами по протоколу ОЛЛ-2009 статистически значимое влияние на безрецидивную выживаемость (относительный риск – HR – 176,9; p<0,0001) и вероятность развития рецидива (HR – 6,4; p=0,02) оказали только два признака – наличие перестроек генов MLL/t(11q23) и c-MYC/t(8q24).
Заключение. Неблагоприятными прогностическими факторами в рамках терапевтического воздействия, предусмотренного протоколом ОЛЛ-2009, являются перестройки генов MLL/t(11q23) и с-MYC/t(8q24). Делеции генов CDKN2A/9p21 и TP53/17p13, численные и комплексные нарушения кариотипа не являются факторами прогноза у взрослых больных Ph-негативным ОЛЛ при использовании протокола ОЛЛ-2009.
Ключевые слова: Ph-негативный острый лимфобластный лейкоз, хромосомные аберрации, протокол ОЛЛ-2009, факторы риска, флуоресцентная гибридизация in situ.
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Materials and methods. The study included 115 adult patients with firstly diagnosed Ph-negative ALL: 58 male and 57 female aged from 15 to 61 years (mean age 26.5 years), who underwent treatment from September 2009 to September 2015 in National Medical Research Center for Hematology MH RF (n=101) and in hematology departments of regional hospitals (n=14). All patients received therapy of ALL-2009 protocol (ClinicalTrials.gov, NCT01193933). The median follow-up was 24.5 months (0.2-94.4 months). As a part of the study results of a standard cytogenetic assay (SCA) were analyzed and fluorescence hybridization in situ (FISH) with the use of DNA-probes was performed on archived biological material for structural changes in gene locuses MLL/t(11q23), с-MYC/t(8q24), TP53/ deletion 17p13, CDKN2A/ deletion 9p21, translocation t(1;19)/E2A-PBX1 и t(12;21)/ETV6-RUNX1; iAMP21 identification.
Results. Karyotype was defined using SCA in 86% of patients. Normal karyotype was found in 48.5% of them, chromosome aberrations in 51.5% (structural changes were found in 19.2%, hyperploidy in 27.2%, and hypoploidy in 5.1%). In 17.2% of patients complex karyotype abnormalities were found. With the use of FISH technique aberrations were found in 67% of patients: 9p21/CDKN2A deletion in 24.3%, MLL/t(11q23) gene abnormalities in 7.8%, 17p13/TP53 deletion in 5.2%, abnormalities of c-MYC/t(8q24) in 1.7%, t(1;19)/E2A-PBX1 in 0.8%, and iAMP21 in 0.8%, other abnormalities (additional signals/absence of signals from gene locuses) in 26.4%, t(12;21)/ETV6-RUNX1 was not found. FISH technique use in addition to SCA allows to increase aberrant karyotype location from 51.5 to 67%. A statistically significant correlation of 9p21/CDKN2A deletion with high serum lactate dehydrogenase activity (p=0.02); MLL/t(11q23) gene abnormalities – with leucocytosis and high blast cells level in blood (p=0.0016), hyperploidy – with normal leukocyte count (p=0.02) was shown. In groups with different cytogenetic abnormalities no statistically significant differences of treatment with ALL-2009 protocol were found (in terms of complete remission, early mortality and treatment resistance). When connection of cytogenetic abnormalities and their combinations with long-term results were analyzed according to ALL-2009 protocol, only two characteristics – MLL/t(11q23) and c-MYC/t(8q24) gene abnormalities had a statistically significant influence on disease-free survival (HR – 176.9; p<0.0001) and chance of recurrence (HR – 6.4; p=0.02)
Conclusion. Adverse prognostic factors in terms of therapeutic management provided in ALL-2009 protocol were MLL/t(11q23) and с-MYC/t(8q24) genes abnormalities. CDKN2A/9p21 and TP53/17p13 genes deletions, quantative and complex karyotype abnormalities were not prognostic factors in adult patients with Ph-negative ALL in ALL-2009 protocol use.
Keywords: Ph-negative acute lymphoblastic leukemia, chromosome aberrations, ALL-2009 protocol, risk factors, FISH.
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14. Slany R. The molecular biology of mixed lineage leukemia. Haematologica. 2009; 94 (7): 984-993. doi:10.3324/haematol.2008.002436
15. Christine J. Harrison, Anthony V. Moorman, Kerry E. Barber, Zoë J. Broadfield, Kan L. Cheung, Rachel L. Harris, G. Reza Jalali, Hazel M. Robinson. Interphase molecular cytogenetic screening for chromosomal abnormalities of prognostic significance in childhood acute lymphoblastic leukemia: a UK Cancer Cytogenetics Group study. Br J Haematol. 2005; 129(4): 520-530. doi: 10.1111/j.1365-2141.2005. 05497.x
16. Johansson B, Moorman AV, Haas OA, Watmore AE, Cheung KL, Swanton S, Secker-Walker LM. on behalf of the European 11q23 Workshop participants. Hematologic malignancies with t(4;11)(q21;q23) – a cytogenetic, morphologic, immunophenotypic and clinical study of 183 cases. European 11q23 Workshop participants. Leukemia. 1998; 12(5): 779-787. doi: 10.1038/sj.leu.2401012
17. Pui CH, Gaynon PS, Boyett JM, Chessells JM, Baruchel A, Kamps W, Silverman LB, Biondi A, Harms DO, Vilmer E, Schrappe M, Camitta B. Outcome of treatment in childhood acute lymphoblastic leukaemia with rearrangements of the 11q23 chromosomal region. Lancet. 2002; 359(9321): 1909-1915. doi: 10.1016/S0140-6736(02)08782-2
18. Raimondi SC, Peiper SC, Kitchingman GR, Behm FG, Williams DL, Hancock ML, Mirro J. Childhood acute lymphoblastic leukemia with chromosomal breakpoints at 11q23. Blood. 1989; 73(6): 1627-1634.
19. Stengel A, Kern W, Haferlach T, Meggendorfer M, Fasan A, Haferlach C. The impact of TP53 mutations and TP53 deletions on survival varies between AML, ALL, MDS and CLL: an analysis of 3307 cases. Leukemia. 2017; 31: 705-711. doi: 10.1038/leu.2016.263
20. Angi M, Kamath V, Yuvarani S, Meena J, Sitaram U, Manipadam MT, Nair S, Ganapule A, Fouzia NA, Abraham A, Viswabandya A, Poonkuzhali B, George B, Mathews V, Srivastava A, Srivastava VM. The t(8;14)(q24.1;q32) and its variant translocations: A study of 34 cases. Hematol Oncol Stem Cell Ther. 2017; 10(3): 126-134. doi: 10.1016/j.hemonc.2017.03.002
21. Harewood L, Robinson H, Harris R, Al Obaidi MJ, Jalali GR, Martineau M, Moorman AV, Sumption N, Richards S, Mitchell C, Harrison CJ. Amplification of AML1 on a duplicated chromosome 21 in acute lymphoblastic leukemia: a study of 20 cases. Leukemia. 2003 (Mar); 17(3): 547-53. doi: 10.1038/sj.leu.2402849
22. Jabbar Al-Obaidi MS, Martineau M, Bennett CF, Franklin IM, Goldstone AH, Harewood L, Jalali GR, Prentice HG, Richards SM, Roberts K, Harrison CJ. ETV6/AML1 fusion by FISH in adult acute lymphoblastic leukemia. Leukemia. 2002; 16(4): 669-674. doi: 10.1038/sj.leu.2402435
2.[Parovichnikova EN, Sokolov AN, Troitskaya VV, Klyasova GA, Rusinov MA, Akhmerzaeva ZKh, Kuz'mina LA, Bondarenko SN, Baranova OY, Kaporskaya TS, Zotina EN, Zinina EE, Samoilova OS, Gavrilova LV, Kaplanov KD, Konstantinova TS, Lapin VA, Kravchenko SK, Gribanova EO, Zvonkov EE, Gavrilina OA, Baskhaeva GA, Galstyan GM, Obukhova TN, Gal'tseva IV, Kulikov SM, Savchenko VG. Acute Ph-negative lymphoblastic leukemias in adults: Risk factors in the use of the ALL-2009 protocol. Ter Arkh. 2016; 88(7):15-24. (In Russ.)]. PMID: 27459610
3. [Parovichnikova EN, Troitskaya VV, Sokolov AN, Agmerzaev ZH, Kuzmina LA, Mendeleeva LP, Klasowa G A, Kravchenko SK, Gribanova EO, Bondarenko SN, Baranov OYu, Kaporskaya T S, Rylova TV, Nizamutdinov AS, Zagoskina TP, Zinin EI, Samoilov OS, Klimovich AV, Karyakina EA, Luferov AS, Gavrilova LV, Konstantinova TS, Toropova IYu, Attack AS, Topilina NA, Tikunova TS, Samarina OP, Kaplanov KD, Obukhova TN, Galtseva IV, Rusyn MA, Kulikov SM, Savchenko VG. Intermediate results on treatment of acute Ph-negative lymphoblastic leukemia in adult patients (results of the Russian research group on treatment of acute lymphoblastic leukemia (RALL)). Hematology. 2014; 9 (3): 6-15. (In Russ.)]. doi: 10.17650/1818-8346-2014-9-3-6-15
4. An International System for Human Cytogenetic Nomenclature. Edit. F.Mitelman. Recommendations of the International Standing Committee on Human Cytogenetic Nomenclature. Publ. in collaboration with Cytogenetics and Cell Genetics. ISCN, 1995.
5. Shih LY, Chou TB, Liang DC, Tzeng YS, Rubnitz JE, Downing JR, Pui CH. Lack of TEL-AML1 fusion transcript resulting from a cryptic t(12;21) in adult B lineage acute lymphoblastic leukemia in Taiwan. Leukemia. 1996; 10(9): 1456-1458. PMID:8751462
6. Mancini M, Scappaticci D, Cimino G, Nanni M, Derme V, Elia L, Tafuri A, Vignetti M, Vitale A, Cuneo A, Castoldi G, Saglio G, Pane F, Mecucci C, Camera A, Specchia G, Tedeschi A, Di Raimondo F, Fioritoni G, Fabbiano F, Marmont F, Ferrara F, Cascavilla N, Todeschini G, Nobile F, Kropp MG, Leoni P, Tabilio A, Luppi M, Annino L, Mandelli F, Foà R. A comprehensive genetic classification of adult acute lymphoblastic leukemia (ALL): analysis of the GIMEMA 0496 protocol. Blood. 2005; 105(9): 3434-3441. doi: 10.1182/blood-2004-07-2922
7. Moorman AV, Harrison CJ, Buck GA, Richards SM, Secker-Walker LM, Martineau M, Vance GH, Cherry AM, Higgins RR, Fielding AK, Foroni L, Paietta E, Tallman MS, Litzow MR, Wiernik PH, Rowe JM, Goldstone AH, Dewald GW. Adult Leukaemia Working Party, Medical Research Council/National Cancer Research Institute. Karyotype is an independent prognostic factor in adult acute lymphoblastic leukemia (ALL): analysis of cytogenetic data from patients treated on the Medical Research Council (MRC) UKALLXII/Eastern Cooperative Oncology Group (ECOG) 2993 trial. Blood. 2007; 109 (8): 3189-3197. doi: 10.1182/blood-2006-10-051912
8. The Groupe Français de Cytogénétique Hématologique. Cytogenetic abnormalities in adult acute lymphoblastic leukemia: correlations with hematologic findings outcome. A Collaborative Study of the Group Français de Cytogénétique Hématologique. Blood. 1996; 87(8): 3135-3142. PMID: 8605327
9. Vey N, Thomas X, Picard C, Kovascovicz T, Charin C, Cayuela JM, Dombret H, Dastugue N, Huguet F, Bastard C, Stamatoulas A, Giollant M, Tournilhac O, Macintyre E, Buzyn A, Bories D, Kuentz M, Dreyfus F, Delannoy A, Raynaud S, Gratecos N, Bordessoule D, de Botton S, Preudhomme C, Reman O, Troussard X, Pigneux A, Bilhou C, Vernant JP, Boucheix C, Gabert J. GET-LALA Group the Swiss Group for Clinical Cancer Research (SAKK). Allogeneic transplantation improves the outcome of adults with t(1;19)/E2A-PBX1 and t(4;11)/MLL-AF4 positive B-cell acute lymphoblastic leukemia: results of the prospective multicenter LALA-94 study. Leukemia. 2006; 20: 2155-2161. doi: 10.1038/sj.leu.2404420
10. Wetzler M, Dodge RK, Mrózek K, Carroll AJ, Tantravahi R, Block AW, Pettenati MJ, Le Beau MM, Frankel SR, Stewart CC, Szatrowski TP, Schiffer CA, Larson RA, Bloomfield CD. Prospective karyotype analysis in adult acute lymphoblastic leukemia: the cancer and leukemia Group B experience. Blood. 1999; 93(11): 3983-3993. PMID: 10339508
11. Na Xu, Yuling Li, Xuan Zhou, Rui Cao, Huan Li, Qi-si Lu, Lin Li, Zi-yuan Lu, Ji-xian Huang, Jing Sun, Qi-fa Liu, Qing-feng Du, Xiao-li Liu. CDKN2 Gene Deletion as Poor Prognosis Predictor Involved in the Progression of Adult BLineage Acute Lymphoblastic Leukemia Patients. Cancer. 2015; 6(11): 1114-1120. doi: 10.7150/jca.11959
12. Anu Usvasalo, Suvi Savola, Riikka Raty, Kim Vettenranta, Arja Harila-Saari, Pirjo Koistinen, Eeva-Riitta Savolainen, Erkki Elonen, Ulla M. Saarinen-Pihkala, Sakari Knuutila. CDKN2A deletions in acute lymphoblastic leukemia of adolescents and young adults – CGH study. Leukemia Research. 2008; 32: 1228-1235. doi: 10.1016/j. leukres.2008.01.014
13. Kim M, Yim S, Cho N, Kang SH, Ko DH, Oh B, Kim TY, Min HJ, She CJ, Kang HJ, Shin HY, Ahn HS, Yoon SS, Kim BK, Shin HR, Han KS, Cho HI, Lee DS. Homozygous deletion of CDKN2A (p16, p14) and CDKN2B (p15) genes is a poor prognostic factor in adult but not in childhood Blineage acute lymphoblastic leukemia: a comparative deletion and hypermethylation study. Cancer Genet Cytogenetic. 2009; 195: 59-65. doi: 10.3892/ol.2016.4169
14. Slany R. The molecular biology of mixed lineage leukemia. Haematologica. 2009; 94 (7): 984-993. doi:10.3324/haematol.2008.002436
15. Christine J. Harrison, Anthony V. Moorman, Kerry E. Barber, Zoë J. Broadfield, Kan L. Cheung, Rachel L. Harris, G. Reza Jalali, Hazel M. Robinson. Interphase molecular cytogenetic screening for chromosomal abnormalities of prognostic significance in childhood acute lymphoblastic leukemia: a UK Cancer Cytogenetics Group study. Br J Haematol. 2005; 129(4): 520-530. doi: 10.1111/j.1365-2141.2005. 05497.x
16. Johansson B, Moorman AV, Haas OA, Watmore AE, Cheung KL, Swanton S, Secker-Walker LM. on behalf of the European 11q23 Workshop participants. Hematologic malignancies with t(4;11)(q21;q23) – a cytogenetic, morphologic, immunophenotypic and clinical study of 183 cases. European 11q23 Workshop participants. Leukemia. 1998; 12(5): 779-787. doi: 10.1038/sj.leu.2401012
17. Pui CH, Gaynon PS, Boyett JM, Chessells JM, Baruchel A, Kamps W, Silverman LB, Biondi A, Harms DO, Vilmer E, Schrappe M, Camitta B. Outcome of treatment in childhood acute lymphoblastic leukaemia with rearrangements of the 11q23 chromosomal region. Lancet. 2002; 359(9321): 1909-1915. doi: 10.1016/S0140-6736(02)08782-2
18. Raimondi SC, Peiper SC, Kitchingman GR, Behm FG, Williams DL, Hancock ML, Mirro J. Childhood acute lymphoblastic leukemia with chromosomal breakpoints at 11q23. Blood. 1989; 73(6): 1627-1634.
19. Stengel A, Kern W, Haferlach T, Meggendorfer M, Fasan A, Haferlach C. The impact of TP53 mutations and TP53 deletions on survival varies between AML, ALL, MDS and CLL: an analysis of 3307 cases. Leukemia. 2017; 31: 705-711. doi: 10.1038/leu.2016.263
20. Angi M, Kamath V, Yuvarani S, Meena J, Sitaram U, Manipadam MT, Nair S, Ganapule A, Fouzia NA, Abraham A, Viswabandya A, Poonkuzhali B, George B, Mathews V, Srivastava A, Srivastava VM. The t(8;14)(q24.1;q32) and its variant translocations: A study of 34 cases. Hematol Oncol Stem Cell Ther. 2017; 10(3): 126-134. doi: 10.1016/j.hemonc.2017.03.002
21. Harewood L, Robinson H, Harris R, Al Obaidi MJ, Jalali GR, Martineau M, Moorman AV, Sumption N, Richards S, Mitchell C, Harrison CJ. Amplification of AML1 on a duplicated chromosome 21 in acute lymphoblastic leukemia: a study of 20 cases. Leukemia. 2003 (Mar); 17(3): 547-53. doi: 10.1038/sj.leu.2402849
22. Jabbar Al-Obaidi MS, Martineau M, Bennett CF, Franklin IM, Goldstone AH, Harewood L, Jalali GR, Prentice HG, Richards SM, Roberts K, Harrison CJ. ETV6/AML1 fusion by FISH in adult acute lymphoblastic leukemia. Leukemia. 2002; 16(4): 669-674. doi: 10.1038/sj.leu.2402435
2. Паровичникова Е.Н., Троицкая В.В., Соколов А.Н., Клясова Г.А., Кузьмина Л.А., Ахмерзаева З.Х., Гаврилина О.А., Басхаева Г.А., Лукьянова И.А. , Кравченко С.К. , Грибанова Е.О. , Бондаренко С.Н., Баранова О.Ю., Капорская Т.С., Рыльцова Т.В., Зотина Т.П., Зинина Е.Е., Самойлова О.С., Елуферьева А.С., Гаврилова Л.В., Константинова Т.С., Лапин В.А., Приступа А.С., Капланов К.Д., Обухова Т.Н. , Гальцева И.В., Русинов М.А., Куликов С.М., Савченко В.Г. Острые Ph-негативные лимфобластные лейкозы взрослых: факторы риска на протоколе ОЛЛ-2009. Терапевтический архив. 2016; 88(7): 15-24. [Parovichnikova EN, Sokolov AN, Troitskaya VV, Klyasova GA, Rusinov MA, Akhmerzaeva ZKh, Kuz'mina LA, Bondarenko SN, Baranova OY, Kaporskaya TS, Zotina EN, Zinina EE, Samoilova OS, Gavrilova LV, Kaplanov KD, Konstantinova TS, Lapin VA, Kravchenko SK, Gribanova EO, Zvonkov EE, Gavrilina OA, Baskhaeva GA, Galstyan GM, Obukhova TN, Gal'tseva IV, Kulikov SM, Savchenko VG. Acute Ph-negative lymphoblastic leukemias in adults: Risk factors in the use of the ALL-2009 protocol. Ter Arkh. 2016; 88(7):15-24. (In Russ.)]. PMID: 27459610
3. Паровичникова Е.Н., Троицкая В.В., Соколов А. Н., Ахмерзаева З.Х., Кузьмина Л. А., Менделеева Л. П., Клясова Г. А., Кравченко С. К., Грибанова Е. О., Бондаренко С. Н., Баранова О. Ю., Капорская Т. С., Рыльцова Т.В., Низамутдинова А.С., Загоскина Т.П., Зинина Е.Е., Самойлова О.С., Климович А.В., Карякина Е.А., Елуферьева А.С., Гаврилова Л.В., Константинова Т.С., Торопова И.Ю., Приступа А.С., Вопилина Н.А., Тикунова Т.С., Скаморина О.П., Капланов К.Д., Обухова Т.Н., Гальцева И.В., Русинов М.А., Куликов С.М., Савченко В.Г. Промежуточные результаты по лечению острых Ph-негативных лимфобластных лейкозов у взрослых больных (итоги Российской исследовательской группы по лечению острых лимфобластных лейкозов (RALL)). Онкогематология. 2014; 9(3): 6-15. [Parovichnikova EN, Troitskaya VV, Sokolov AN, Agmerzaev ZH, Kuzmina LA, Mendeleeva LP, Klasowa G A, Kravchenko SK, Gribanova EO, Bondarenko SN, Baranov OYu, Kaporskaya T S, Rylova TV, Nizamutdinov AS, Zagoskina TP, Zinin EI, Samoilov OS, Klimovich AV, Karyakina EA, Luferov AS, Gavrilova LV, Konstantinova TS, Toropova IYu, Attack AS, Topilina NA, Tikunova TS, Samarina OP, Kaplanov KD, Obukhova TN, Galtseva IV, Rusyn MA, Kulikov SM, Savchenko VG. Intermediate results on treatment of acute Ph-negative lymphoblastic leukemia in adult patients (results of the Russian research group on treatment of acute lymphoblastic leukemia (RALL)). Hematology. 2014; 9 (3): 6-15. (In Russ.)]. doi: 10.17650/1818-8346-2014-9-3-6-15
4. An International System for Human Cytogenetic Nomenclature. Edit. F.Mitelman. Recommendations of the International Standing Committee on Human Cytogenetic Nomenclature. Publ. in collaboration with Cytogenetics and Cell Genetics. ISCN, 1995.
5. Shih LY, Chou TB, Liang DC, Tzeng YS, Rubnitz JE, Downing JR, Pui CH. Lack of TEL-AML1 fusion transcript resulting from a cryptic t(12;21) in adult B lineage acute lymphoblastic leukemia in Taiwan. Leukemia. 1996; 10(9): 1456-1458. PMID:8751462
6. Mancini M, Scappaticci D, Cimino G, Nanni M, Derme V, Elia L, Tafuri A, Vignetti M, Vitale A, Cuneo A, Castoldi G, Saglio G, Pane F, Mecucci C, Camera A, Specchia G, Tedeschi A, Di Raimondo F, Fioritoni G, Fabbiano F, Marmont F, Ferrara F, Cascavilla N, Todeschini G, Nobile F, Kropp MG, Leoni P, Tabilio A, Luppi M, Annino L, Mandelli F, Foà R. A comprehensive genetic classification of adult acute lymphoblastic leukemia (ALL): analysis of the GIMEMA 0496 protocol. Blood. 2005; 105(9): 3434-3441. doi: 10.1182/blood-2004-07-2922
7. Moorman AV, Harrison CJ, Buck GA, Richards SM, Secker-Walker LM, Martineau M, Vance GH, Cherry AM, Higgins RR, Fielding AK, Foroni L, Paietta E, Tallman MS, Litzow MR, Wiernik PH, Rowe JM, Goldstone AH, Dewald GW. Adult Leukaemia Working Party, Medical Research Council/National Cancer Research Institute. Karyotype is an independent prognostic factor in adult acute lymphoblastic leukemia (ALL): analysis of cytogenetic data from patients treated on the Medical Research Council (MRC) UKALLXII/Eastern Cooperative Oncology Group (ECOG) 2993 trial. Blood. 2007; 109 (8): 3189-3197. doi: 10.1182/blood-2006-10-051912
8. The Groupe Français de Cytogénétique Hématologique. Cytogenetic abnormalities in adult acute lymphoblastic leukemia: correlations with hematologic findings outcome. A Collaborative Study of the Group Français de Cytogénétique Hématologique. Blood. 1996; 87(8): 3135-3142. PMID: 8605327
9. Vey N, Thomas X, Picard C, Kovascovicz T, Charin C, Cayuela JM, Dombret H, Dastugue N, Huguet F, Bastard C, Stamatoulas A, Giollant M, Tournilhac O, Macintyre E, Buzyn A, Bories D, Kuentz M, Dreyfus F, Delannoy A, Raynaud S, Gratecos N, Bordessoule D, de Botton S, Preudhomme C, Reman O, Troussard X, Pigneux A, Bilhou C, Vernant JP, Boucheix C, Gabert J. GET-LALA Group the Swiss Group for Clinical Cancer Research (SAKK). Allogeneic transplantation improves the outcome of adults with t(1;19)/E2A-PBX1 and t(4;11)/MLL-AF4 positive B-cell acute lymphoblastic leukemia: results of the prospective multicenter LALA-94 study. Leukemia. 2006; 20: 2155-2161. doi: 10.1038/sj.leu.2404420
10. Wetzler M, Dodge RK, Mrózek K, Carroll AJ, Tantravahi R, Block AW, Pettenati MJ, Le Beau MM, Frankel SR, Stewart CC, Szatrowski TP, Schiffer CA, Larson RA, Bloomfield CD. Prospective karyotype analysis in adult acute lymphoblastic leukemia: the cancer and leukemia Group B experience. Blood. 1999; 93(11): 3983-3993. PMID: 10339508
11. Na Xu, Yuling Li, Xuan Zhou, Rui Cao, Huan Li, Qi-si Lu, Lin Li, Zi-yuan Lu, Ji-xian Huang, Jing Sun, Qi-fa Liu, Qing-feng Du, Xiao-li Liu. CDKN2 Gene Deletion as Poor Prognosis Predictor Involved in the Progression of Adult BLineage Acute Lymphoblastic Leukemia Patients. Cancer. 2015; 6(11): 1114-1120. doi: 10.7150/jca.11959
12. Anu Usvasalo, Suvi Savola, Riikka Raty, Kim Vettenranta, Arja Harila-Saari, Pirjo Koistinen, Eeva-Riitta Savolainen, Erkki Elonen, Ulla M. Saarinen-Pihkala, Sakari Knuutila. CDKN2A deletions in acute lymphoblastic leukemia of adolescents and young adults – CGH study. Leukemia Research. 2008; 32: 1228-1235. doi: 10.1016/j. leukres.2008.01.014
13. Kim M, Yim S, Cho N, Kang SH, Ko DH, Oh B, Kim TY, Min HJ, She CJ, Kang HJ, Shin HY, Ahn HS, Yoon SS, Kim BK, Shin HR, Han KS, Cho HI, Lee DS. Homozygous deletion of CDKN2A (p16, p14) and CDKN2B (p15) genes is a poor prognostic factor in adult but not in childhood Blineage acute lymphoblastic leukemia: a comparative deletion and hypermethylation study. Cancer Genet Cytogenetic. 2009; 195: 59-65. doi: 10.3892/ol.2016.4169
14. Slany R. The molecular biology of mixed lineage leukemia. Haematologica. 2009; 94 (7): 984-993. doi:10.3324/haematol.2008.002436
15. Christine J. Harrison, Anthony V. Moorman, Kerry E. Barber, Zoë J. Broadfield, Kan L. Cheung, Rachel L. Harris, G. Reza Jalali, Hazel M. Robinson. Interphase molecular cytogenetic screening for chromosomal abnormalities of prognostic significance in childhood acute lymphoblastic leukemia: a UK Cancer Cytogenetics Group study. Br J Haematol. 2005; 129(4): 520-530. doi: 10.1111/j.1365-2141.2005. 05497.x
16. Johansson B, Moorman AV, Haas OA, Watmore AE, Cheung KL, Swanton S, Secker-Walker LM. on behalf of the European 11q23 Workshop participants. Hematologic malignancies with t(4;11)(q21;q23) – a cytogenetic, morphologic, immunophenotypic and clinical study of 183 cases. European 11q23 Workshop participants. Leukemia. 1998; 12(5): 779-787. doi: 10.1038/sj.leu.2401012
17. Pui CH, Gaynon PS, Boyett JM, Chessells JM, Baruchel A, Kamps W, Silverman LB, Biondi A, Harms DO, Vilmer E, Schrappe M, Camitta B. Outcome of treatment in childhood acute lymphoblastic leukaemia with rearrangements of the 11q23 chromosomal region. Lancet. 2002; 359(9321): 1909-1915. doi: 10.1016/S0140-6736(02)08782-2
18. Raimondi SC, Peiper SC, Kitchingman GR, Behm FG, Williams DL, Hancock ML, Mirro J. Childhood acute lymphoblastic leukemia with chromosomal breakpoints at 11q23. Blood. 1989; 73(6): 1627-1634.
19. Stengel A, Kern W, Haferlach T, Meggendorfer M, Fasan A, Haferlach C. The impact of TP53 mutations and TP53 deletions on survival varies between AML, ALL, MDS and CLL: an analysis of 3307 cases. Leukemia. 2017; 31: 705-711. doi: 10.1038/leu.2016.263
20. Angi M, Kamath V, Yuvarani S, Meena J, Sitaram U, Manipadam MT, Nair S, Ganapule A, Fouzia NA, Abraham A, Viswabandya A, Poonkuzhali B, George B, Mathews V, Srivastava A, Srivastava VM. The t(8;14)(q24.1;q32) and its variant translocations: A study of 34 cases. Hematol Oncol Stem Cell Ther. 2017; 10(3): 126-134. doi: 10.1016/j.hemonc.2017.03.002
21. Harewood L, Robinson H, Harris R, Al Obaidi MJ, Jalali GR, Martineau M, Moorman AV, Sumption N, Richards S, Mitchell C, Harrison CJ. Amplification of AML1 on a duplicated chromosome 21 in acute lymphoblastic leukemia: a study of 20 cases. Leukemia. 2003 (Mar); 17(3): 547-53. doi: 10.1038/sj.leu.2402849
22. Jabbar Al-Obaidi MS, Martineau M, Bennett CF, Franklin IM, Goldstone AH, Harewood L, Jalali GR, Prentice HG, Richards SM, Roberts K, Harrison CJ. ETV6/AML1 fusion by FISH in adult acute lymphoblastic leukemia. Leukemia. 2002; 16(4): 669-674. doi: 10.1038/sj.leu.2402435
________________________________________________
2.[Parovichnikova EN, Sokolov AN, Troitskaya VV, Klyasova GA, Rusinov MA, Akhmerzaeva ZKh, Kuz'mina LA, Bondarenko SN, Baranova OY, Kaporskaya TS, Zotina EN, Zinina EE, Samoilova OS, Gavrilova LV, Kaplanov KD, Konstantinova TS, Lapin VA, Kravchenko SK, Gribanova EO, Zvonkov EE, Gavrilina OA, Baskhaeva GA, Galstyan GM, Obukhova TN, Gal'tseva IV, Kulikov SM, Savchenko VG. Acute Ph-negative lymphoblastic leukemias in adults: Risk factors in the use of the ALL-2009 protocol. Ter Arkh. 2016; 88(7):15-24. (In Russ.)]. PMID: 27459610
3. [Parovichnikova EN, Troitskaya VV, Sokolov AN, Agmerzaev ZH, Kuzmina LA, Mendeleeva LP, Klasowa G A, Kravchenko SK, Gribanova EO, Bondarenko SN, Baranov OYu, Kaporskaya T S, Rylova TV, Nizamutdinov AS, Zagoskina TP, Zinin EI, Samoilov OS, Klimovich AV, Karyakina EA, Luferov AS, Gavrilova LV, Konstantinova TS, Toropova IYu, Attack AS, Topilina NA, Tikunova TS, Samarina OP, Kaplanov KD, Obukhova TN, Galtseva IV, Rusyn MA, Kulikov SM, Savchenko VG. Intermediate results on treatment of acute Ph-negative lymphoblastic leukemia in adult patients (results of the Russian research group on treatment of acute lymphoblastic leukemia (RALL)). Hematology. 2014; 9 (3): 6-15. (In Russ.)]. doi: 10.17650/1818-8346-2014-9-3-6-15
4. An International System for Human Cytogenetic Nomenclature. Edit. F.Mitelman. Recommendations of the International Standing Committee on Human Cytogenetic Nomenclature. Publ. in collaboration with Cytogenetics and Cell Genetics. ISCN, 1995.
5. Shih LY, Chou TB, Liang DC, Tzeng YS, Rubnitz JE, Downing JR, Pui CH. Lack of TEL-AML1 fusion transcript resulting from a cryptic t(12;21) in adult B lineage acute lymphoblastic leukemia in Taiwan. Leukemia. 1996; 10(9): 1456-1458. PMID:8751462
6. Mancini M, Scappaticci D, Cimino G, Nanni M, Derme V, Elia L, Tafuri A, Vignetti M, Vitale A, Cuneo A, Castoldi G, Saglio G, Pane F, Mecucci C, Camera A, Specchia G, Tedeschi A, Di Raimondo F, Fioritoni G, Fabbiano F, Marmont F, Ferrara F, Cascavilla N, Todeschini G, Nobile F, Kropp MG, Leoni P, Tabilio A, Luppi M, Annino L, Mandelli F, Foà R. A comprehensive genetic classification of adult acute lymphoblastic leukemia (ALL): analysis of the GIMEMA 0496 protocol. Blood. 2005; 105(9): 3434-3441. doi: 10.1182/blood-2004-07-2922
7. Moorman AV, Harrison CJ, Buck GA, Richards SM, Secker-Walker LM, Martineau M, Vance GH, Cherry AM, Higgins RR, Fielding AK, Foroni L, Paietta E, Tallman MS, Litzow MR, Wiernik PH, Rowe JM, Goldstone AH, Dewald GW. Adult Leukaemia Working Party, Medical Research Council/National Cancer Research Institute. Karyotype is an independent prognostic factor in adult acute lymphoblastic leukemia (ALL): analysis of cytogenetic data from patients treated on the Medical Research Council (MRC) UKALLXII/Eastern Cooperative Oncology Group (ECOG) 2993 trial. Blood. 2007; 109 (8): 3189-3197. doi: 10.1182/blood-2006-10-051912
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Авторы
И.С. ПИСКУНОВА, Т.Н. ОБУХОВА, Е.Н. ПАРОВИЧНИКОВА, С.М. КУЛИКОВ, В.В. ТРОИЦКАЯ, О.А. ГАВРИЛИНА, В.Г. САВЧЕНКО
ФГБУ «Национальный медицинский исследовательский центр гематологии» Минздрава России, Москва, Россия
National Research Center for Hematology, Moscow, Russia
ФГБУ «Национальный медицинский исследовательский центр гематологии» Минздрава России, Москва, Россия
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National Research Center for Hematology, Moscow, Russia
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