Acute megakaryocytic leukemia with acquired trisomy 21 and structural chromosomal rearrangements in a young child
https://doi.org/10.35754/0234-5730-2024-69-1-104-111
Abstract
Introduction. There are two main subgroups of acute megakaryocytic leukemia (AMKL): with and without Down syndrome (DS). In children, AMKL without DS is a rare disease that is often associated with a rearrangement of the NUP98, KMT2A (MLL) genes, sporadic translocations identified both as the only abnormalities and as part of a complex karyotype, early onset of the disease and extremely unfavorable clinical outcome.
Aim: to present a clinical case of AMKL in a girl without DS with acquired trisomy 21, der(5)t(1;5)(q23-25;q35) and t(3;8) (q21;q24).
Main findings. A clinical case of a patient who was diagnosed with AMKL without DS at the age of 1 year and 5 months, accompanied by hepatosplenomegaly, lymphadenopathy, with a rapidly progressive course and lack of response to chemotherapy is described. A standard cytogenetic study revealed acquired trisomy 21, as well as clonal secondary chromosomal rearrangements — der(5)t(1;5)(q23-25;q35) and t(3;8)(q21;q24). The revealed structural aberrations have not yet been described in children with AMKL. The presented observation shows that der(5)t(1;5)(q23-25;q35) and t(3;8)(q21;q24) in combination with acquired trisomy 21 in young children with AMKL may be factors of poor prognosis.
Keywords
acute megakaryocytic leukemia,
standard cytogenetic examination,
trisomy 21,
additional chromosomal rearrangements
Supporting agencies: the study was supported by the Republican Specialized Scientifi c and Practical Medical Center of Hematology of the Ministry of Health of the Republic of Uzbekistan.
About the Authors
Yu. Yu. Assesorova
Republican Specialized Scientific and Practical Medical Center of Hematology of the Ministry of Health of the Republic of Uzbekistan
Uzbekistan
Uzbekistan
Yuliana Yu. Assesorova, Cand. Sci. (Biol.), laboratory doctor, Molecular Genetics and Cytogenetics Lab
Tashkent
M. S. Islamov
Republican Specialized Scientific and Practical Medical Center of Hematology of the Ministry of Health of the Republic of Uzbekistan
Uzbekistan
Uzbekistan
Miralisher S. Islamov, Dr. Sci. (Med.), director
Tashkent
L. K. Mustafina
Republican Specialized Scientific and Practical Medical Center of Hematology of the Ministry of Health of the Republic of Uzbekistan
Uzbekistan
Uzbekistan
Liya K. Mustafina, laboratory doctor, Molecular Genetics and Cytogenetics Lab
Tashkent
A. R. Klevleeva
Pediatric Hematology Department of the Center for Pediatric Hematology, Oncology and Clinical Immunology of the Ministry of Health of the Republic of Uzbekistan
Uzbekistan
Uzbekistan
Albina R. Klevleeva, physician
Tashkent
References
1. Qi H., Mao Y., Cao Q., et al. Clinical Characteristics and Prognosis of 27 Patients with Childhood Acute Megakaryoblastic Leukemia. Med Sci Monit. 2020; 26: e922662. DOI: 10.12659/MSM.922662.
2. Li J., Kalev-Zylinska M.L. Advances in molecular characterization of pediatric acute megakaryoblastic leukemia not associated with Down syndrome; impact on therapy development. Front Cell Dev Biol. 2023; 11: 1170622. DOI: 10.3389/fcell.2023.1170622.
3. Dima D., Oprita L., Rosu A.M., et al. Adult acute megakaryoblastic leukemia: rare association with cytopenias of undetermined signifi cance and p210 and p190 BCR-ABL transcripts. Onco Targets Ther. 2017; 10: 5047–51. DOI: 10.2147/OTT.S146973.
4. Giri S., Pathak R., Prouet P., et al. Acute megakaryocytic leukemia is associated with worse outcomes than other types of acute myeloid leukemia. Blood. 2014; 124(25): 3833–4. DOI: 10.1182/blood-2014-09-603415.
5. Schweitzer J., Zimmermann M., Rasche M., et al. Improved outcome of pediatric patients with acute megakaryoblastic leukemia in the AML-BFM 04 trial. Ann Hematol. 2015; 94(8): 1327–36. DOI: 10.1007/s00277-015-2383-2.
6. de Rooij J.D., Branstetter C., Ma J., et al. Pediatric non-Down syndrome acute megakaryoblastic leukemia is characterized by distinct genomic subsets with varying outcomes. Nat Genet. 2017; 49(3): 451–6. DOI: 10.1038/ng.3772.
7. Zhang A., Liu L., Zong S., et al. Pediatric non-Down’s syndrome acute megakaryoblastic leukemia patients in China: A single center’s real-world analysis. Front Oncol. 2022; 12: 940725. DOI: 10.3389/fonc.2022.940725.
8. Gruber T.A., Downing J.R. The biology of pediatric acute megakaryoblastic leukemia. Blood. 2015 Aug; 126(8): 943–9. DOI: 10.1182/blood-2015-05-567859.
9. Maarouf N., Mahmoud S., Khedr R., et al. Outcome of Childhood Acute Megakaryoblastic Leukemia: Children’s Cancer Hospital Egypt 57357 Experience. Clin Lymphoma Myeloma Leuk. 2019; 19(3): e142–52. DOI: 10.1016/j.clml.2018.12.011.
10. Huang J., Hu G., Suo P., et al. Unmanipulated haploidentical hematopoietic stem cell transplantation for pediatric de novo acute megakaryoblastic leukemia without Down syndrome in China: A single-center study. Front Oncol. 2023; 13: 1116205. DOI: 10.3389/fonc.2023.1116205.
11. Creutzig U., van den Heuvel-Eibrink M.M., Gibson B., et al. Diagnosis and management of acute myeloid leukemia in children and adolescents: recommendations from an international expert panel. Blood. 2012; 120(16): 3187–205. DOI: 10.1182/blood-2012-03-362608.
12. Calvo C., Fenneteau O., Leverger G., et al. Infant Acute Myeloid Leukemia: A Unique Clinical and Biological Entity. Cancers (Basel). 2021; 13(4): 777. DOI: 10.3390/cancers13040777.
13. Inaba H., Zhou Y., Abla O., et al. Heterogeneous cytogenetic subgroups and outcomes in childhood acute megakaryoblastic leukemia: a retrospective international study. Blood. 2015; 126(13): 1575–84. DOI: 10.1182/blood-2015-02-629204.
14. Feng J., Leung A.W.K., Cheng F.W.T., et al. t(1;22)(p13;q13) Acute Megakaryoblastic Leukemia Complicated by Hepatic Fibrosis: Antifi brosis Therapy? J Pediatr Hematol Oncol. 2021; 43(8): e1164–7. DOI: 10.1097/MPH.0000000000001986.
15. Tosi S., Mostafa Kamel Y., Owoka T., et al. Paediatric acute myeloid leukaemia with the t(7;12)(q36;p13) rearrangement: a review of the biological and clinical management aspects. Biomark Res. 2015; 3: 21. DOI: 10.1186/s40364-015-0041-4.
16. Ragusa D., Dijkhuis L., Pina C., Tosi S. Mechanisms associated with t(7;12) acute myeloid leukaemia: from genetics to potential treatment targets. Biosci Rep. 2023; 43(1): BSR20220489. DOI: 10.1042/BSR20220489.
17. McNulty M., Crispino J.D. Acute Megakaryocytic Leukemia. Cold Spring Harb Perspect Med. 2020 Feb 3; 10(2): a034884. DOI: 10.1101/cshperspect.a034884.
18. Chou S.T., Opalinska J.B., Yao Y., et al. Trisomy 21 enhances human fetal erythro-megakaryocytic development. Blood. 2008; 112(12): 4503–6. DOI: 10.1182/blood-2008-05-157859.
19. Tunstall-Pedoe O., Roy A., Karadimitris A., et al. Abnormalities in the myeloid progenitor compartment in Down syndrome fetal liver precede acquisition of GATA1 mutations. Blood. 2008; 112(12): 4507–11. DOI: 10.1182/blood-2008-04-152967.
20. De Vita S., Devoy A., Groet J., et al. Megakaryocyte hyperproliferation without GATA1 mutation in foetal liver of a case of Down syndrome with hydrops foetalis. Br J Haematol. 2008; 143(2): 300–3. DOI: 10.1111/j.1365-2141.2008.07332.x.
21. Rougemont A.L., Makrythanasis P., Finci V., et al. Myeloid proliferation without GATA1 mutations in a fetus with Down syndrome presenting in utero as a pericardial effusion. Pediatr Dev Pathol. 2010; 13(5): 423–6. DOI: 10.2350/09-11-0743-CR.1.
22. Nižetić D., Groet J. Tumorigenesis in Down’s syndrome: big lessons from a small chromosome. Nat Rev Cancer. 2012; 12(10): 721–32. DOI: 10.1038/nrc3355.
23. Soad Al Bahar, Zamecnikova A. der(5)t(1;5)(q12-q25;q13-q35). Atlas Genet Cytogenet Oncol Haematol. 2016-02-01. Online version: http://atlasgeneticsoncology.org/haematological/1646/der(5)t(1;5)(q12-q25;q13-q35).
24. Moassass F., Wafa A., Liehr T., et al. Down syndrome associated childhood myeloid leukemia with yet unreported acquired chromosomal abnormalities and a new potential adverse marker: dup(1)(q25q44). Mol Cytogenet. 2018; 11: 22. DOI: 10.1186/s13039-018-0370-8.
25. Jean-Loup Huret. t(3;8)(q21;q24) in myeloid malignancies. Atlas Genet Cytogenet Oncol Haematol. 2008-06-01. Online version: http://atlasgeneticsoncology.org/haematological/1249/t(3;8)(q21;q24)-in-myeloid-malignancies.
Review
For citations:
Assesorova Yu.Yu., Islamov M.S., Mustafina L.K., Klevleeva A.R. Acute megakaryocytic leukemia with acquired trisomy 21 and structural chromosomal rearrangements in a young child. Russian journal of hematology and transfusiology. 2024;69(1):104-111. (In Russ.) https://doi.org/10.35754/0234-5730-2024-69-1-104-111
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