Document Type : Original Article(s)
Authors
- Mahshid Heidary Sadegh 1
- Maniya Mozafari 2
- Mohammad Vasei 3
- Sajjadeh Movahedinia 2
- Marzieh Hosseini 4
- Moeinadin Safavi 2
1 Department of Pathology, Tehran University of Medical Sciences, Tehran, Iran
2 Department of Molecular Pathology and Cytogenetic, Children’s Medical Center Hospital, Tehran University of Medical Sciences, Tehran, Iran
3 Gene Therapy Research Center, Digestive Disease research Institute, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran
4 Department of Molecular Pathology and Cytogenetic, Shiraz University of Medical Sciences, Shiraz, Iran
Abstract
Background: Acute myeloid leukemia (AML) accounts for 15%-20% of childhood leukemia. A variety of cytogenetic abnormalities have been reported in AML, but it is still debated how these alterations affect patient survival and outcome. We aimed to evaluate the cytogenetic abnormalities of pediatric AML in association with prognosis.
Method: In this retrospective cross-sectional study, 46 cases of pediatric AML, diagnosed using French-American-British (FAB) criteria, admitted to a referral center during 2018-2023, who had not yet received chemotherapy, were included. Patients were evaluated for cytogenetic alterations by bone marrow karyotyping and polymerase chain reaction molecular methods. Patients were followed up to evaluate overall survival and recurrence-free survival. Data were analyzed using SPSS software version 23 and chi-square, Mann-Whitney, t-test and Kaplan-Meier tests. P < 0.05 was considered significant.
Results: Totally, 19 of 46 (41.3%) patients showed cytogenetic abnormalities. The prevalence of numerical and structural abnormalities was 23.9% and 28.3%, respectively. The most common numerical changes included monosomy 7, loss of chromosome Y, and trisomy 21, as order. The most common structural variants included t(v;11), t(15;17), t(8;21) and del(7q). Those with t(8;21) and t(15;17) or absence of cytogenetic abnormalities had a lower recurrence and death rate as compared with those with unfavorable cytogenetic abnormalities (P = 0.007, P = 0.002 respectively). White blood cell count was significantly lower in patients with numerical cytogenetic abnormalities than those without.
Conclusion: Cytogenetic abnormalities were rather common in pediatric AML. Monosomy 7/del(7q) and chromosome 11 alteration were the most common cytogenetic abnormalities. Presence of abnormalities, other than those known as favorable, were associated with worse survival.
Highlights
Moeinadin Safavi (Google Scholar)
Keywords
Main Subjects
This article has been accepted for publication and undergone full peer review but has not been through the copyediting, typesetting, pagination, and proofreading process, which may lead to differences between this version and the Version of Record. Please cite this article as doi: 10.30476/mejc.2024.100660.2002
- Kantarjian H, Kadia T, DiNardo C, Daver N, Borthakur G, Jabbour E, et al. Acute myeloid leukemia: current progress and future directions. Blood Cancer J. 2021;11(2):41. doi: 10.1038/s41408-021-00425-3.
- Lins MM, Mello MJG, Ribeiro RC, De Camargo B, de Fátima Pessoa Militão de Albuquerque M, Thuler LCS. Survival and risk factors for mortality in pediatric patients with acute myeloid leukemia in a single reference center in low-middle-income country. Ann Hematol. 2019;98(6):1403-11. doi: 10.1007/s00277-019-03661-7.
- Løhmann DJ, Abrahamsson J, Ha SY, Jónsson Ó G, Koskenvuo M, Lausen B, et al. Effect of age and body weight on toxicity and survival in pediatric acute myeloid leukemia: results from NOPHO-AML 2004. Haematologica. 2016;101(11):1359-67.doi: 10.3324/haematol.2016.146175.
- Tomizawa D, Tsujimoto SI. Risk-stratified therapy for pediatric acute myeloid leukemia. Cancers (Basel). 2023;15(16):4171. doi: 10.3390/cancers15164171.
- Tosic N, Marjanovic I, Lazic J. Pediatric acute myeloid leukemia: Insight into genetic landscape and novel targeted approaches. Biochem Pharmacol. 2023;215:115705. doi: 10.1016/j.bcp.2023.115705.
- Conneely SE, Stevens AM. Acute myeloid leukemia in children: emerging paradigms in genetics and new approaches to therapy. Curr Oncol Rep. 2021;23(2):16. doi: 10.1007/s11912-020-01009-3.
- Reinhardt D, Antoniou E, Waack K. Pediatric acute myeloid leukemia-past, present, and future. J Clin Med. 2022;11(3):504. doi: 10.3390/jcm11030504.
- Pasquer H, Tostain M, Kaci N, Roux B, Benajiba L. Descriptive and functional genomics in acute myeloid leukemia (AML): paving the road for a cure. Cancers. 2021;13(4):748.
- Conneely SE, Rau RE. The genomics of acute myeloid leukemia in children. Cancer Metastasis Rev. 2020;39(1):189-209.doi: 10.1007/s10555-020-09846-1.
- Grinev VV, Barneh F, Ilyushonak IM, Nakjang S, Smink J, van Oort A, et al. RUNX1/RUNX1T1 mediates alternative splicing and reorganises the transcriptional landscape in leukemia. Nature Communications. 2021;12(1):520. doi: 10.1038/s41467-020-20848-z.
- Shi LH, Ma P, Liu JS, Li Y, Wang YF, Guo MF, et al. Current views of chromosomal abnormalities in pediatric acute myeloid leukemia (AML). Eur Rev Med Pharmacol Sci. 2017;21(4 Suppl):25-30.
- Creutzig U, Zimmermann M, Reinhardt D, Rasche M, von Neuhoff C, Alpermann T, et al. Changes in cytogenetics and molecular genetics in acute myeloid leukemia from childhood to adult age groups. Cancer. 2016;122(24):3821-30.doi: 10.1002/cncr.30220.
- Saultz JN, Garzon R. Acute myeloid leukemia: a concise review. J Clin Med. 2016;5(3):33. doi: 10.3390/jcm5030033.
- Boscaro E, Urbino I, Catania FM, Arrigo G, Secreto C, Olivi M, et al. Modern risk stratification of acute myeloid leukemia in 2023: integrating established and emerging prognostic factors. Cancers. 2023;15(13):3512.
- Chen W, Yang J, Chen P. Cytogenetic characteristics of and prognosis for acute myeloid leukemia in 107 children. Asian Biomed (Res Rev News). 2021;15(2):79-89.doi: 10.2478/abm-2021-0010.
- Nunes AL, Paes CA, Murao M, Viana MB, De Oliveira BM. Cytogenetic abnormalities, WHO classification, and evolution of children and adolescents with acute myeloid leukemia. Hematol Transfus Cell Ther. 2019;41(3):236-43.doi: 10.1016/j.htct.2018.09.007.
- Arber DA, Orazi A, Hasserjian R, Thiele J, Borowitz MJ, Le Beau MM, et al. The 2016 revision to the World Health Organization classification of myeloid neoplasms and acute leukemia. Blood. 2016;127(20):2391-405. doi: 10.1182/blood-2016-03-643544.
- Chen X, Wang X, Dou H, Yang Z, Bi J, Huang Y, et al. Cytogenetic and mutational analysis and outcome assessment of a cohort of 284 children with de novo acute myeloid leukemia reveal complex karyotype as an adverse risk factor for inferior survival. Mol Cytogenet. 2021;14(1):27. doi: 10.1186/s13039-021-00547-0.
- Safaei A, Shokripour M, Omidifar N. Bone marrow and karyotype findings of patients with pancytopenia in southern Iran. Iran J Med Sci. 2014;39(4):333-40.
- Arsham MS, Barch MJ, Lawce HJ, editors. Association of Genetic T The AGT cytogenetics laboratory manual. 4th ed. New Jersey, Hoboken: Wiley Blackwell; 2017. 1168p.
- Quessada J, Cuccuini W, Saultier P, Loosveld M, Harrison CJ, Lafage-Pochitaloff M. Cytogenetics of pediatric acute myeloid leukemia: a review of the current knowledge. Genes (Basel). 2021;12(6) :924. doi: 10.3390/genes12060924.
- Khoury JD, Solary E, Abla O, Akkari Y, Alaggio R, Apperley JF, 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.
- Sandahl JD, Kjeldsen E, Abrahamsson J, Ha SY, Heldrup J, Jahnukainen K, et al. Ploidy and clinical characteristics of childhood acute myeloid leukemia: A NOPHO-AML study. Genes Chromosomes Cancer. 2014;53(8):667-75.doi: 10.1002/gcc.22177.
- Meena JP, Pathak N, Gupta AK, Bakhshi S, Gupta R, Makkar H, et al. Molecular evaluation of gene mutation profiles and copy number variations in pediatric acute myeloid leukemia. Leuk Res. 2022;122:106954. doi: 10.1016/j.leukres.2022.106954.
- Harrison CJ, Hills RK, Moorman AV, Grimwade DJ, Hann I, Webb DK, et al. Cytogenetics of childhood acute myeloid leukemia: United Kingdom Medical Research Council Treatment trials AML 10 and 12. J Clin Oncol. 2010;28(16):2674-81. doi: 10.1200/jco.2009.24.8997.
- Tarlock K, Meshinchi S. Pediatric acute myeloid leukemia: biology and therapeutic implications of genomic variants. Pediatr Clin North Am. 2015;62(1):75-93. doi: 10.1016/j.pcl.2014.09.007.
- Hasle H, Alonzo TA, Auvrignon A, Behar C, Chang M, Creutzig U, et al. Monosomy 7 and deletion 7q in children and adolescents with acute myeloid leukemia: an international retrospective study. Blood. 2007;109(11):4641-7. doi: 10.1182/blood-2006-10-051342.
- Balgobind BV, Raimondi SC, Harbott J, Zimmermann M, Alonzo TA, Auvrignon A, et al. Novel prognostic subgroups in childhood 11q23/MLL-rearranged acute myeloid leukemia: results of an international retrospective study. Blood. 2009;114(12):2489-96. doi: 10.1182/blood-2009-04-215152.
- Yuen KY, Liu Y, Zhou YZ, Wang Y, Zhou DH, Fang JP, et al. Mutational landscape and clinical outcome of pediatric acute myeloid leukemia with 11q23/KMT2A rearrangements. Cancer Med. 2023;12(2):1418-30. doi: 10.1002/cam4.5026.
- Ksiazek T, Czogala M, Kaczowka P, Sadowska B, Pawinska-Wasikowska K, Bik-Multanowski M, et al. High frequency of fusion gene transcript resulting from t(10;11)(p12;q23) translocation in pediatric acute myeloid leukemia in Poland. Front Pediatr. 2020;8:278. doi: 10.3389/fped.2020.00278.
- Meena JP, Makkar H, Gupta AK, Bakhshi S, Gupta R, Thakral D, et al. A comprehensive analysis of cytogenetics, molecular profile, and survival among pediatric acute myeloid leukemia: a prospective study from a tertiary referral center. Am J Blood Res. 2022;12(6):177-89.
)