Молекулярные методы оценки нестабильности опухолевого генома при остром миелоидном лейкозе
https://doi.org/10.17650/1818-8346-2025-20-3-69-75
Аннотация
Лабораторная диагностика острых миелоидных лейкозов позволяет грамотно стратифицировать больных на группы риска согласно современным классификациям и подобрать персонифицированное лечение. Однако в каждой группе прогноза все равно развиваются рецидивы заболевания и констатируются рефрактерные формы. Некоторые цитогенетические и молекулярные аберрации не могут быть обнаружены с помощью стандартных методов диагностики. Новые, современные лабораторные методы потенциально могут выявить механизмы рефрактерности опухоли, а также новые мишени для таргетной терапии, что может улучшить диагностику и прогноз больных острым миелоидным лейкозом.
Об авторах
Д. К. Бессмертный
ФГБУ «Национальный медицинский исследовательский центр гематологии» Минздрава России
Россия
Россия
Дмитрий Константинович Бессмертный
125167 Москва, Новый Зыковский пр-д, 4
З. Т. Фидарова
ФГБУ «Национальный медицинский исследовательский центр гематологии» Минздрава России
Россия
Россия
125167 Москва, Новый Зыковский пр-д, 4
Список литературы
1. Döhner H., Wei A.H., Appelbaum F.R. et al. Diagnosis and management of AML in adults: 2022 recommendations from an international expert panel on behalf of the ELN. Blood 2022;140(12):1345–77. DOI: 10.1182/blood.2022016867
2. Bullinger L., Krönke J., Schön C. et al. Identification of acquired copy number alterations and uniparental disomies in cytogenetically normal acute myeloid leukemia using high-resolution singlenucleotide polymorphism analysis. Leukemia 2010;24(2):438–49. DOI: 10.1038/leu.2009.263
3. Khoury J.D., Solary E., Abla O. et al. The 5th edition of the World Health Organization Classification of Haematolymphoid Tumours: Myeloid and Histiocytic/Dendritic Neoplasms. Leukemia 2022;36(7):1703–19. DOI: 10.1038/s41375-022-01613-1
4. Tallman M.S., Wang E.S., Altman J.K. et al. Acute Myeloid Leukemia, Version 3.2019, NCCN Clinical Practice Guidelines in Oncology. J Natl Compr Canc Netw 2019;17(6):721–49. DOI: 10.6004/jnccn.2019.0028
5. Akkari Y.M.N., Baughn L.B., Dubuc A.M. et al. Guiding the global evolution of cytogenetic testing for hematologic malignancies. Blood 2022;139(15):2273–84. DOI: 10.1182/blood.2021014309
6. Lo M.Y., Tsai C.H., Kuo Y.Y. et al. Prognostic relevance of adult acute myeloid leukemia patients according to the 2022 European Leukemianet Risk Stratification. Blood 2022;140(Suppl 1):130–1. DOI: 10.1182/blood-2022-168522
7. Li H., Zimmerman S.E., Weyemi U. Genomic instability and metabolism in cancer. Int Rev Cell Mol Biol 2021;364:241–65. DOI: 10.1016/BS.IRCMB.2021.05.004
8. Targa A., Rancati G. Cancer: a CINful evolution. Curr Opin Cell Biol 2018;52:136–44. DOI: 10.1016/j.ceb.2018.03.007
9. Bakhoum S.F., Kabeche L., Murnane J.P. et al. DNA-damage response during mitosis induces whole-chromosome missegregation. Cancer Discov 2014;4(11):1281–9. DOI: 10.1158/2159-8290.CD-14-0403
10. Venkatesan S., Natarajan A.T., Hande M.P. Chromosomal instability – mechanisms and consequences. Mutat Res Genet Toxicol Environ Mutagen 2015;793:176–84. DOI: 10.1016/J.MRGENTOX.2015.08.008
11. Hoevenaar W.H.M., Janssen A., Quirindongo A.I. et al. Degree and site of chromosomal instability define its oncogenic potential. Nat Commun 2020;11(1):1501. DOI: 10.1038/s41467-020-15279-9
12. Compton D.A. Mechanisms of aneuploidy. Curr Opin Cell Biol 2011;23(1):109–13. DOI: 10.1016/j.ceb.2010.08.007
13. Hitzler J.K., Zipursky A. Origins of leukaemia in children with Down syndrome. Nat Rev Cancer 2005;5(1):11–20. DOI: 10.1038/nrc1525
14. Thompson S.L., Compton D.A. Proliferation of aneuploid human cells is limited by a p53-dependent mechanism. J Cell Biol 2010;188(3):369–81. DOI: 10.1083/jcb.200905057
15. Lal R., Lind K., Heitzer E. et al. Somatic TP53 mutations characterize preleukemic stem cells in acute myeloid leukemia. Blood 2017;129(18):2587–91. DOI: 10.1182/blood-2016-11-751008
16. Fontana M.C., Marconi G., Feenstra J.D.M. et al. Chromothripsis in acute myeloid leukemia: biological features and impact on survival. Leukemia 2018;32(7):1609–20. DOI: 10.1038/s41375-018-0035-y
17. Rausch T., Jones D.T., Zapatka M. et al. Genome sequencing of pediatric medulloblastoma links catastrophic DNA rearrangements with TP53 mutations. Cell 2012;148(1–2):59–71. DOI: 10.1016/j.cell.2011.12.013
18. Qiu Z., Zhang Z., Roschke A. et al. Generation of gross chromosomal rearrangements by a single engineered DNA double strand break. Sci Rep 2017;7(1):43156. DOI: 10.1038/srep43156
19. Khan F.A., Ali S.O. Physiological roles of DNA double-strand breaks. J Nucleic Acids 2017;2017:6439169. DOI: 10.1155/2017/6439169
20. Jacoby M.A., De Jesus Pizarro R.E., Shao J. et al. The DNA double-strand break response is abnormal in myeloblasts from patients with therapy-related acute myeloid leukemia. Leukemia 2014;28(6):1242–51. DOI: 10.1038/leu.2013.368
21. De Lange T. Shelterin: the protein complex that shapes and safeguards human telomeres. Genes Dev 2005;19(18):2100–10. DOI: 10.1101/gad.1346005
22. Mosrati M.A., Willander K., Falk I.J. et al. Association between TERT promoter polymorphisms and acute myeloid leukemia risk and prognosis. Oncotarget 2015;6(28):25109–20. DOI: 10.18632/oncotarget.4668
23. Yan S., Han B., Wu Y. et al. Telomerase gene mutation screening and telomere overhang detection in Chinese patients with acute myeloid leukemia. Leuk Lymphoma 2013;54(7):1437–41. DOI: 10.3109/10428194.2012.729834
24. Sun Y., Chen B.-R., Deshpande A. Epigenetic regulators in the development, maintenance, and therapeutic targeting of acute myeloid leukemia. Front Oncol 2018;8:41. DOI: 10.3389/fonc.2018.00041
25. Wang J., He N., Wang R. et al. Analysis of TET2 and EZH2 gene functions in chromosome instability in acute myeloid leukemia. Sci Rep 2020;10(1):2706. DOI: 10.1038/s41598-020-59365-w
26. Mrózek K., Eisfeld A.K., Kohlschmidt J. et al. Complex karyotype in de novo acute myeloid leukemia: typical and atypical subtypes differ molecularly and clinically. Leukemia 2019;33(7):1620–34. DOI: 10.1038/s41375-019-0390-3
27. Forghieri F., Comoli P., Marasca R. et al. Minimal/measurable residual disease monitoring in NPM1-mutated acute myeloid leukemia: a clinical viewpoint and perspectives. Int J Mol Sci 2018;19(11):3492. DOI: 10.3390/ijms19113492
28. Hause R.J., Pritchard C.C., Shendure J., Salipante S.J. Classification and characterization of microsatellite instability across 18 cancer types. Nat Med 2017;22(11):1342–50. DOI: 10.1038/nm.4191
29. Nomdedéu J.F., Perea G., Estivill C. et al. Microsatellite instability is not an uncommon finding in adult de novo acute myeloid leukemia. Ann Hematol 2005;84(6):368–75. DOI: 10.1007/s00277-005-1035-3
30. El Hussein S., Daver N., Liu J.L. et al. Microsatellite instability assessment by immunohistochemistry in acute myeloid leukemia: a reappraisal and review of the literature. Clin Lymphoma Myeloma Leuk 2022;22(6):e386–91. DOI: 10.1016/j.clml.2021.12.004
31. Bates S.E. Classical cytogenetics: karyotyping techniques. Methods Mol Biol 2011;767:177–90. DOI: 10.1007/978-1-61779-201-4_13
32. Bayani J., Squire J.A. Fluorescence in situ hybridization (FISH). Curr Protoc Cell Biol 2004;22:Unit22.4. DOI: 10.1002/0471143030.cb2204s23
33. Hart S.M., Foroni L. Core binding factor genes and human leukemia. Haematologica 2002;87(12):1307–23.
34. Mrózek K., Heerema N.A., Bloomfield C.D. Cytogenetics in acute leukemia. Blood Rev 2004;18(2):115–36. DOI: 10.1016/S0268-960X(03)00040-7
35. Marcucci G., Mrózek K., Ruppert A.S. et al. Prognostic factors and outcome of core binding factor acute myeloid leukemia patients with t(8;21) differ from those of patients with inv(16): a Cancer and Leukemia Group B study. J Clin Oncol 2005;23(24):5705–17. DOI: 10.1200/JCO.2005.15.610
36. Grimwade D., Walker H., Harrison G. et al. The predictive value of hierarchical cytogenetic classification in older adults with acute myeloid leukemia (AML): analysis of 1065 patients entered into the United Kingdom Medical Research Council AML11 trial. Blood 2001;98(5):1312–20. DOI: 10.1182/blood.v98.5.1312
37. Weinberg O.K., Siddon A., Madanat Y.F. et al. TP53 mutation defines a unique subgroup within complex karyotype de novo and therapy-related MDS/AML. Blood Adv 2022;6(9):2847–53. DOI: 10.1182/bloodadvances.2021006239
38. Meyer C., Burmeister T., Gröger D. et al. The MLL recombinome of acute leukemias in 2017. Leukemia 2018;32(2):273–84. DOI: 10.1038/leu.2017.213
39. Lugthart S., Gröschel S., Beverloo H.B. et al. Clinical, molecular, and prognostic significance of WHO type inv(3)(q21q26.2)/t(3;3) (q21;q26.2) and various other 3q abnormalities in acute myeloid leukemia. J Clin Oncol 2010;28(24):3890–8. DOI: 10.1200/JCO.2010.29.2771
40. Wang J., Zheng J., Lee E.E. et al. A cloud-based resource for genome coordinate-based exploration and large-scale analysis of chromosome aberrations and gene fusions in cancer. Genes Chromosomes Cancer 2023;62(8):441–8. DOI: 10.1002/gcc.23128
41. Slovak M.L., Gundacker H., Bloomfield C.D. et al. A retrospective study of 69 patients with t(6;9)(p23;q34) AML emphasizes the need for a prospective, multicenter initiative for rare “poor prognosis” myeloid malignancies. Leukemia 2006;20(7):1295–7. DOI: 10.1038/sj.leu.2404233
42. Garibyan L., Avashia N. Polymerase chain reaction. J Invest Dermatol 2013;133(3):1–4. DOI: 10.1038/jid.2013.1
43. Lorenz T.C. Polymerase chain reaction: basic protocol plus troubleshooting and optimization strategies. J Vis Exp 2012;(63):e3998. DOI: 10.3791/3998
44. Ossenkoppele G., Schuurhuis G.J. MRD in AML: does it already guide therapy decision-making? Hematology Am Soc Hematol Educ Program 2016;2016(1):356–65. DOI: 10.1182/asheducation-2016.1.356
45. Лобанова Т.И., Гальцева И.В., Паровичникова Е.Н. Исследование минимальной остаточной болезни у пациентов с острыми миелоидными лейкозами методом многоцветной проточной цитофлуориметрии (обзор литературы). Онкогематология 2018;13(1):83–102. DOI: 10.17650/1818-8346-2018-13-1-83-102
46. Кашлакова А.И., Паровичникова Е.Н., Бидерман Б.В. и др. Определение молекулярно-генетического профиля у взрослых больных острыми миелоидными лейкозами методом секвенирования нового поколения. Гематология и трансфузиология 2020;65(4):444–59. DOI: 10.35754/0234-5730-2020-65-4-444-459
47. Mareschal S., Palau A., Lindberg J. et al. Challenging conventional karyotyping by next-generation karyotyping in 281 intensively treated patients with AML. Blood Adv 2021;5(4):1003–16. DOI: 10.1182/bloodadvances.2020002517
48. Höllein A., Nadarajah N., Meggendorfer M. et al. Molecular characterization of AML with RUNX1‐RUNX1T1 at diagnosis and relapse reveals net loss of co‐mutations. Hemasphere 2019;3(1):e178. DOI: 10.1097/HS9.0000000000000178
49. Morita K., Wang F., Jahn K. et al. Clonal evolution of acute myeloid leukemia revealed by high-throughput single-cell genomics. Nat Commun 2020;11(1):5327. DOI: 10.1038/s41467-020-19119-8
50. Кашлакова А.И., Бидерман Б.В., Паровичникова Е.Н. Клональное кроветворение и острые миелоидные лейкозы. Онкогематология 2023;18(3):92–101. DOI: 10.17650/1818-8346-2023-18-3-92-101
51. Falini B., Brunetti L., Sportoletti P., Martelli M.P. NPM1-mutated acute myeloid leukemia: from bench to bedside. Blood 2020;136(15):1707–21. DOI: 10.1182/blood.2019004226
52. Gorello P., Cazzaniga G., Alberti F. et al. Quantitative assessment of minimal residual disease in acute myeloid leukemia carrying nucleophosmin (NPM1) gene mutations. Leukemia 2006;20(6):1103–8. DOI: 10.1038/sj.leu.2404149
53. Tiong I.S., Dillon R., Ivey A. et al. The natural history of NPM1MUT measurable residual disease (MRD) positivity after completion of chemotherapy in acute myeloid leukemia (AML). Blood 2020;136(Suppl 1):25–7. DOI: 10.1182/blood-2020-140296
54. Kottaridis P.D., Gale R.E., Frew M.E. et al. The presence of a FLT3 internal tandem duplication in patients with acute myeloid leukemia (AML) adds important prognostic information to cytogenetic risk group and response to the first cycle of chemotherapy: analysis of 854 patients from the United Kingdom Medical Research Council AML 10 and 12 trials. Blood 2001;98(6):1752–9. DOI: 10.1182/blood.V98.6.1752
55. Lin M.T., Tseng L.H., Beierl K. et al. Tandem Duplication PCR. Diagn Mol Pathol 2013;22(3):149–55. DOI: 10.1097/PDM.0b013e31828308a1
56. He R., Devine D.J., Tu Z.J. et al. Hybridization capture-based next generation sequencing reliably detects FLT3 mutations and classifies FLT3-internal tandem duplication allelic ratio in acute myeloid leukemia: a comparative study to standard fragment analysis. Mod Pathol 2020;33(3):334–43. DOI: 10.1038/s41379-019-0359-9
57. Schlenk R.F., Weber D., Fiedler W. et al. Midostaurin added to chemotherapy and continued single-agent maintenance therapy in acute myeloid leukemia with FLT3-ITD. Blood 2019;133(8): 840–51. DOI: 10.1182/blood-2018-08-869453
58. Batzir N.A., Shohat M., Maya I. Chromosomal microarray analysis (CMA) a clinical diagnostic tool in the prenatal and postnatal settings. Pediatr Endocrinol Rev 2015;13(1):448–54.
59. Zhang C., Cerveira E., Romanovitch M., Zhu Q. Array-based comparative genomic hybridization (aCGH). Methods Mol Biol 2017;1541:167–79. DOI: 10.1007/978-1-4939-6703-2_15
60. Grimwade D., Mrózek K. Diagnostic and prognostic value of cytogenetics in acute myeloid leukemia. Hematol Oncol Clin North Am 2011;25(6):1135–61, vii. DOI: 10.1016/j.hoc.2011.09.018
61. Ibáñez M., Such E., Onecha E. et al. Analysis of SNP array abnormalities in patients with de novo acute myeloid leukemia with normal karyotype. Sci Rep 2020;10(1):5904. DOI: 10.1038/s41598-020-61589-9
62. Walker C.J., Kohlschmidt J., Eisfeld A.K. et al. Genetic characterization and prognostic relevance of acquired uniparental disomies in cytogenetically normal acute myeloid leukemia. Clin Cancer Res 2019;25(21):6524–31. DOI: 10.1158/1078-0432.CCR-19-0725
63. Ronaghy A., Yang R.K., Khoury J.D., Kanagal-Shamanna R. Clinical applications of chromosomal microarray testing in myeloid malignancies. Curr Hematol Malig Rep 2020;15(3):194–202. DOI: 10.1007/s11899-020-00578-1
64. Gronseth C.M., McElhone S.E., Storer B.E. et al. Prognostic significance of acquired copy-neutral loss of heterozygosity in acute myeloid leukemia. Cancer 2015;121(17):2900–8. DOI: 10.1002/CNCR.29475
65. Mak A.C., Lai Y.Y., Lam E.T. et al. Genome-wide structural variation detection by genome mapping on nanochannel arrays. Genetics 2016;202(1):351–62. DOI: 10.1534/genetics.115.183483
66. Levy B., Baughn L.B., Akkari Y. et al. Optical genome mapping in acute myeloid leukemia: a multicenter evaluation. Blood Adv 2023;7(7):1297–307. DOI: 10.1182/bloodadvances.2022007583
67. Balducci E., Kaltenbach S., Villarese P. et al. Optical genome mapping refines cytogenetic diagnostics, prognostic stratification and provides new molecular insights in adult MDS/AML patients. Blood Cancer J 2022;12(9):126. DOI: 10.1038/s41408-022-00718-1
Рецензия
Для цитирования:
Бессмертный Д.К., Фидарова З.Т. Молекулярные методы оценки нестабильности опухолевого генома при остром миелоидном лейкозе. Онкогематология. 2025;20(3):69-75. https://doi.org/10.17650/1818-8346-2025-20-3-69-75
For citation:
Bessmertnyy D.K., Fidarova Z.T. Molecular methods for assessing tumor genome instability in acute myeloid leukemia. Oncohematology. 2025;20(3):69-75. (In Russ.) https://doi.org/10.17650/1818-8346-2025-20-3-69-75
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