vestimИзвестия Национальной академии наук Беларуси. Серия медицинских наукProceedings of the National Academy of Sciences of Belarus, Medical series1814-60232524-2350The Republican Unitary Enterprise Publishing House "Belaruskaya Navuka"vestim-321Research ArticleКЛИНИЧЕСКАЯ И ЭКСПЕРИМЕНТАЛЬНАЯ МЕДИЦИНАCLINICAL AND EXPERIMENTAL MEDICINEВЛИЯНИЕ МОЛЕКУЛЯРНО-ГЕНЕТИЧЕСКИХ ИЗМЕНЕНИЙ НА ПРОГНОЗ ПРИ ОСТРОМ МИЕЛОИДНОМ ЛЕЙКОЗЕ У ДЕТЕЙEFFECT OF MOLECULAR GENETIC CHANGES ON THE PROGNOSIS IN CASE OF ACUTE MYELOID LEUKEMIA IN CHILDRENБАРОВСКАЯЮ. А.BAROUSKAYAYu. A.ju1ia@tut.byСТЕГАНЦЕВАМ. В.STEGANTSEVAM. V.КУСТАНОВИЧА. М.КUSTANOVICHA. M.САВИЦКАЯТ. В.SAVITSKAYAT. V.АЛЕЙНИКОВАО. В.ALEINIKOVO. V.Республиканский научно-практический центр детской онкологииBelarusian Research Center for Pediatric Oncology, Hematology and Immunology201619112016035764Copyright © БАРОВСКАЯ Ю.А., СТЕГАНЦЕВА М.В., КУСТАНОВИЧ А.М., САВИЦКАЯ Т.В., АЛЕЙНИКОВА О.В., 20162016БАРОВСКАЯ Ю.А., СТЕГАНЦЕВА М.В., КУСТАНОВИЧ А.М., САВИЦКАЯ Т.В., АЛЕЙНИКОВА О.В.BAROUSKAYA Y.A., STEGANTSEVA M.V., КUSTANOVICH A.M., SAVITSKAYA T.V., ALEINIKOV O.V.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://vestimed.belnauka.by/jour/article/view/321

Целью данного исследования являлся анализ прогностического значения молекулярно- генетических изменений при остром миелоидном лейкозе (ОМЛ) у детей, получавших лечение в Республике Беларусь по оригинальным протоколам ОМЛ-ММ-2000 и ОМЛ-ММ-2006. Наличие inv(16) и t(8; 21) при ОМЛ ассоциировано с благоприятным исходом. Показатели выживаемости пациентов с t(1; 11) сравнимы с таковыми в группе CBF, что также позволяет отнести данную аномалию к прогностически благоприятной. Риск развития рецидива у пациентов с t(10; 11) выше, чем у остальной когорты 11q23. Прогностическое влияние на исход болезни у лиц с нормальным кариотипом оказывает наличие либо отсутствие дополнительных генетических событий.

The main goal of this research is to analyze the prognostic significance of molecular genetic changes in case of AML (acute myeloid leukemia) in children treated in the Republic of Belarus under original AML-MM-2000 and AML-MM-2006 protocols. The presence of inv(16) and t(8; 21) in AML is related to a favorable outcome. The survival index among patients with t(1; 11) is comparable to the CBF group, which also allows us to qualify such abnormality as with the favorable prognosis. The risk of relapse among patients with t(10; 11) is higher than among the rest of 11q23 cohort. The presence or the absence of any additional genetic events has a prognostic impact on the clinical outcome for patients with normal karyotype.

острый миелоидный лейкоздетимолекулярно-генетические измененияпрогнозacute myeloid leukemiachildrenmolecular genetic changesprognosisReferencesPediatric AML: From Biology to Clinical Management / J. D. de Rooij [et al.] // J. Clin. Med. – 2015. – Vol. 4, N 1. – P. 127–149.Pediatric AML: From Biology to Clinical Management / J. D. de Rooij [et al.] // J. Clin. Med. – 2015. – Vol. 4, N 1. – P. 127–149.Rubnitz, J. E. Childhood Acute Myeloid Leukaemia / J. E. Rubnitz, H. Inaba // Br. J. of Haematol. – 2012. – Vol. 159, N 3. – P. 259–276.Rubnitz, J. E. Childhood Acute Myeloid Leukaemia / J. E. Rubnitz, H. Inaba // Br. J. of Haematol. – 2012. – Vol. 159, N 3. – P. 259–276.Гук, Л. Г. Анализ мутаций в генах FLT3, KIT, MLL, NPM1 у детей с острым миелоидным лейкозом: автореф. дис. ... канд. мед. наук: 14.01.21 / Фед. науч.-клин. центр детск. гематол., онколог. и иммунол. – М., 2010. – 28 с.Гук, Л. Г. Анализ мутаций в генах FLT3, KIT, MLL, NPM1 у детей с острым миелоидным лейкозом: автореф. дис. ... канд. мед. наук: 14.01.21 / Фед. науч.-клин. центр детск. гематол., онколог. и иммунол. – М., 2010. – 28 с.Gilliland, D. G. Molecular genetics of human leukemias: new insights into therapy / D. J. Gilliland // Semin. Hematol. – 2002. – Vol. 39, N 4. – P. 6–11.Gilliland, D. G. Molecular genetics of human leukemias: new insights into therapy / D. J. Gilliland // Semin. Hematol. – 2002. – Vol. 39, N 4. – P. 6–11.Takahashi, S. Сurrent findings for recurring mutations in acute myeloid leukemia / S. Takahashi // J. of Hematol. and Oncol. – 2011. – Vol. 4, N 36. – P. 1–11.Takahashi, S. Сurrent findings for recurring mutations in acute myeloid leukemia / S. Takahashi // J. of Hematol. and Oncol. – 2011. – Vol. 4, N 36. – P. 1–11.Cytogenetics of childhood acute myeloid leukemia: United Kingdom Med. Res. Council Treatment Trials AML 10 and 12 / C. J. Harrison [et al.] // J. Clin. Oncol. – 2010. – Vol. 28. – P. 2674–2681.Cytogenetics of childhood acute myeloid leukemia: United Kingdom Med. Res. Council Treatment Trials AML 10 and 12 / C. J. Harrison [et al.] // J. Clin. Oncol. – 2010. – Vol. 28. – P. 2674–2681.Prognostic impact of specific chromosomal aberrations in a large group of pediatric patients with acute myeloid leukemia treated uniformly according to trial AML-BFM 98 / C. von Neuhoff [et al.] // J. Clin. Oncol. – 2010. – Vol. 28. – P. 2682–2689.Prognostic impact of specific chromosomal aberrations in a large group of pediatric patients with acute myeloid leukemia treated uniformly according to trial AML-BFM 98 / C. von Neuhoff [et al.] // J. Clin. Oncol. – 2010. – Vol. 28. – P. 2682–2689.Integrative analysis of type-I and type-II aberrations underscores the genetic heterogeneity of pediatric acute myeloid leukemia / B. V. Вalgobind [et al.] // Haematologica. – 2011. – Vol. 96. – P. 1478–1487.Integrative analysis of type-I and type-II aberrations underscores the genetic heterogeneity of pediatric acute myeloid leukemia / B. V. Вalgobind [et al.] // Haematologica. – 2011. – Vol. 96. – P. 1478–1487.Faulk, K. Overview of therapy and strategies for optimizing outcomes in de novo pediatric acute myeloid leukemia / K. Faulk, L. Gore, T. Сooper // Pediatric Drugs. – 2014. – Vol. 16, N 3. – P. 213–227.Faulk, K. Overview of therapy and strategies for optimizing outcomes in de novo pediatric acute myeloid leukemia / K. Faulk, L. Gore, T. Сooper // Pediatric Drugs. – 2014. – Vol. 16, N 3. – P. 213–227.Rubnitz, J. E. How I treat pediatric acute myeloid leukemia / J. E. Rubnitz // Blood. – 2012. – Vol. 119, N 25. – P. 5980–5988.Rubnitz, J. E. How I treat pediatric acute myeloid leukemia / J. E. Rubnitz // Blood. – 2012. – Vol. 119, N 25. – P. 5980–5988.Characterization of CEBPA mutations and promoterhypermethylation in pediatric acute myeloid leukemia / I. H. Hollink [et al.] // Haematologica. – 2011. – Vol. 96. – P. 384–392.Characterization of CEBPA mutations and promoterhypermethylation in pediatric acute myeloid leukemia / I. H. Hollink [et al.] // Haematologica. – 2011. – Vol. 96. – P. 384–392.Marcucci, G. Molecular genetics of adult acute myeloid leukemia: prognostic and therapeutic implications / G. Marcucci, T. Haferlach, H. Döhner // J. Clin. Oncol. – 2011. – Vol. 29, N 5. – P. 475–486.Marcucci, G. Molecular genetics of adult acute myeloid leukemia: prognostic and therapeutic implications / G. Marcucci, T. Haferlach, H. Döhner // J. Clin. Oncol. – 2011. – Vol. 29, N 5. – P. 475–486.Prevalence and prognostic implications of CEBPA mutations in pediatric acute myeloid leukemia (AML): a report from the Children’s Oncology Group / P. A. Ho [et al.] // Blood. – 2009. – Vol. 113, N 26. – P. 6558–6566.Prevalence and prognostic implications of CEBPA mutations in pediatric acute myeloid leukemia (AML): a report from the Children’s Oncology Group / P. A. Ho [et al.] // Blood. – 2009. – Vol. 113, N 26. – P. 6558–6566.Mapping epigenetic regulator gene mutations in cytogenetically normal pediatric acute myeloid leukemia / D. G. Valerio [et al.] // Haematologica. – 2014. – Vol. 99, N 8. – P. 130– 132.Mapping epigenetic regulator gene mutations in cytogenetically normal pediatric acute myeloid leukemia / D. G. Valerio [et al.] // Haematologica. – 2014. – Vol. 99, N 8. – P. 130– 132.Integrative analysis of type-I and type-II aberrations underscores the genetic heterogeneity of pediatric acute myeloid leukemia / B. Balgobind [et al.] // Haematologica. – 2011. – Vol. 96, N 10. – P. 1478–1487.Integrative analysis of type-I and type-II aberrations underscores the genetic heterogeneity of pediatric acute myeloid leukemia / B. Balgobind [et al.] // Haematologica. – 2011. – Vol. 96, N 10. – P. 1478–1487.Pui, C.-H. Biology, risk stratification and therapy of pediatric acute leukemias: an update / C.-H. Pui, W. Carroll, S. Meshinchi // J. Clin. Oncol. – 2011. – Vol. 29, N 5. – P. 551–565.Pui, C.-H. Biology, risk stratification and therapy of pediatric acute leukemias: an update / C.-H. Pui, W. Carroll, S. Meshinchi // J. Clin. Oncol. – 2011. – Vol. 29, N 5. – P. 551–565.Diagnosis and management of acute myeloid leukemia in children and adolescents: recommendations from an international expert panel / U. Creutzig [et al.] // Blood. – 2012. – Vol. 120, N 16. – P. 3187–3205.Diagnosis and management of acute myeloid leukemia in children and adolescents: recommendations from an international expert panel / U. Creutzig [et al.] // Blood. – 2012. – Vol. 120, N 16. – P. 3187–3205.Rassi, F. Update on optimal management of acute myeloid leukemia / F. Rassi, M. Arellano // Clin. Med. Insights: Oncology. – 2013. – Vol. 7. – P. 181–197.Rassi, F. Update on optimal management of acute myeloid leukemia / F. Rassi, M. Arellano // Clin. Med. Insights: Oncology. – 2013. – Vol. 7. – P. 181–197.Paschka, P. Сore-binding factor acute myeloid leukemia: can we improve on HiDAC consolidation? / P. Paschka, K. Dohner // Hematology. – 2013. – Vol. 2013, N 1. – P. 209–219.Paschka, P. Сore-binding factor acute myeloid leukemia: can we improve on HiDAC consolidation? / P. Paschka, K. Dohner // Hematology. – 2013. – Vol. 2013, N 1. – P. 209–219.Prognostic impact of c-KIT mutations in core binding factor leukemias: an Ital. retrospective study / R. Сairoli [et al.] // Blood. – 2006. – Vol. 107, N 9. – P. 3463–3468.Prognostic impact of c-KIT mutations in core binding factor leukemias: an Ital. retrospective study / R. Сairoli [et al.] // Blood. – 2006. – Vol. 107, N 9. – P. 3463–3468.Incidence and prognostic impact of c-Kit, FLT3, and Ras gene mutations in core binding factor acute myeloid leukemia (CBF-AML) / N. Boissel [et al.] // Leukemia. – 2006. – Vol. 20, N 6. – P. 965–970.Incidence and prognostic impact of c-Kit, FLT3, and Ras gene mutations in core binding factor acute myeloid leukemia (CBF-AML) / N. Boissel [et al.] // Leukemia. – 2006. – Vol. 20, N 6. – P. 965–970.Prevalence and prognostic significance of KIT mutations in pediatric patients with core binding factor AML enrolled on serial pediatric cooperative trials for de novo AML / J. A. Pollard [et al.] // Blood. – 2010. – Vol. 115, N 12. – P. 2372–2379.Prevalence and prognostic significance of KIT mutations in pediatric patients with core binding factor AML enrolled on serial pediatric cooperative trials for de novo AML / J. A. Pollard [et al.] // Blood. – 2010. – Vol. 115, N 12. – P. 2372–2379.Characterization of CEBPA mutations and promoterhypermethylation in pediatric acute myeloid leukemia / I. H. Hollink [et al.] // Haematologica. – 2011. – Vol. 96, N 3. – P. 384–392.Characterization of CEBPA mutations and promoterhypermethylation in pediatric acute myeloid leukemia / I. H. Hollink [et al.] // Haematologica. – 2011. – Vol. 96, N 3. – P. 384–392.Marcucci, G. Molecular genetics of adult acute myeloid leukemia: prognostic and therapeutic implications / G. Marcucci, T. Haferlach, H. Döhner // J. Clin. Oncol. – 2011. – Vol. 29, N 5. – P. 475–486.Marcucci, G. Molecular genetics of adult acute myeloid leukemia: prognostic and therapeutic implications / G. Marcucci, T. Haferlach, H. Döhner // J. Clin. Oncol. – 2011. – Vol. 29, N 5. – P. 475–486.Prevalence and prognostic implications of CEBPA mutations in pediatric acute myeloid leukemia (AML): a report from the Children’s Oncology Group / P. A. Ho [et al.] // Blood. – 2009. – Vol. 113, N 26. – P. 6558–6566.Prevalence and prognostic implications of CEBPA mutations in pediatric acute myeloid leukemia (AML): a report from the Children’s Oncology Group / P. A. Ho [et al.] // Blood. – 2009. – Vol. 113, N 26. – P. 6558–6566.Gene mutation patterns and their prognostic impact in a cohort of 1185 patients with acute myeloid leukemia / Y. Shen [et al.] // Blood. – 2011. – Vol. 118, N 20. – P. 5593–5603.Gene mutation patterns and their prognostic impact in a cohort of 1185 patients with acute myeloid leukemia / Y. Shen [et al.] // Blood. – 2011. – Vol. 118, N 20. – P. 5593–5603.Сooperating gene mutations in childhood acute myeloid leukemia with special reference on mutations of ASXL1, TET2, IDH1, IDH2, and DNMT3 / D.-C. Liang [et al.] // Blood. – 2013. – Vol. 121, N 15. – P. 2988–2995.Сooperating gene mutations in childhood acute myeloid leukemia with special reference on mutations of ASXL1, TET2, IDH1, IDH2, and DNMT3 / D.-C. Liang [et al.] // Blood. – 2013. – Vol. 121, N 15. – P. 2988–2995.Creutzig, U. Diagnosis and management of acute myeloid leukemia in children and adolescents: recommendations from an international expert panel / U. Creutzig, M. M. van den Heuvel-Eibrink, B. Gibson // Blood. – 2012. – Vol. 120, N 16. – P. 3187–3205.Creutzig, U. Diagnosis and management of acute myeloid leukemia in children and adolescents: recommendations from an international expert panel / U. Creutzig, M. M. van den Heuvel-Eibrink, B. Gibson // Blood. – 2012. – Vol. 120, N 16. – P. 3187–3205.Standardized RT-PCR analysis of fusion gene transcripts from chromosome aberrations in acute leukemia for detection of minimal residual disease. Report of the BIOMED-1 Concerted Action: investigation of minimal residual disease in acute leukemia / J. van Dongen [et al.] // Leukemia. – 1999. – Vol. 13, N 12. – P. 1901–1928.Standardized RT-PCR analysis of fusion gene transcripts from chromosome aberrations in acute leukemia for detection of minimal residual disease. Report of the BIOMED-1 Concerted Action: investigation of minimal residual disease in acute leukemia / J. van Dongen [et al.] // Leukemia. – 1999. – Vol. 13, N 12. – P. 1901–1928.Kaplan, E. Nonparametric Estimation from Incomplete Observations / E. Kaplan, P. Meier // J. of the Am. Stat. Association. – 1958. – Vol. 53, N 282. – P. 457–481.Kaplan, E. Nonparametric Estimation from Incomplete Observations / E. Kaplan, P. Meier // J. of the Am. Stat. Association. – 1958. – Vol. 53, N 282. – P. 457–481.Gooley, T. Estimation of failure probabilities in the presence of competing risks: new representations of old estimators / T. Gooley, W. Leisenring, J. Crowley // Statistics in Medicine. – 1999. – Vol. 18, N 6. – P. 695–706.Gooley, T. Estimation of failure probabilities in the presence of competing risks: new representations of old estimators / T. Gooley, W. Leisenring, J. Crowley // Statistics in Medicine. – 1999. – Vol. 18, N 6. – P. 695–706.Gray, R. A class of K-sample tests for comparing the cumulative incidence of a competing risk / R. Gray // The Annals of Statistics. – 1988. – Vol. 16, N 3. – P. 1140–1154.Gray, R. A class of K-sample tests for comparing the cumulative incidence of a competing risk / R. Gray // The Annals of Statistics. – 1988. – Vol. 16, N 3. – P. 1140–1154.Clinical and genetic characteristics of acute myeloid leukemia with t(8; 21) in children and results of therapy according to protocol AML-MM-2000 / I. Kalinina [et al.] // Onkogematologiya. – 2011. – Vol. 6, N 1. – P. 11–18.Clinical and genetic characteristics of acute myeloid leukemia with t(8; 21) in children and results of therapy according to protocol AML-MM-2000 / I. Kalinina [et al.] // Onkogematologiya. – 2011. – Vol. 6, N 1. – P. 11–18.

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