Vol. 21 No. 1 (2022)
Original Articles

Apoptosis in myelodysplasia: Association with patient age, bone marrow cellularity and karyotypes

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  • Daiane C. de Souza,
  • Adriana C. Camargo,
  • Eliane F. Rodrigues,
  • Mércia M. Campos,
  • Tatiana F. Alvarenga,
  • Cecília de S. Fernandez,
  • Elaine S. da Costa,
  • Teresa de S. Fernandez
DOI: https://doi.org/10.12957/bjhbs.2022.68177

Published 2022-07-04

Keywords

  • Myelodysplastic syndrome,
  • Apoptosis,
  • Patient age,
  • Bone marrow cellularity,
  • Karyotypes

How to Cite

1.
C. de Souza D, C. Camargo A, F. Rodrigues E, M. Campos M, F. Alvarenga T, de S. Fernandez C, S. da Costa E, de S. Fernandez T. Apoptosis in myelodysplasia: Association with patient age, bone marrow cellularity and karyotypes . BJHBS [Internet]. 2022 Jul. 4 [cited 2024 Oct. 11];21(1):21-30. Available from: https://bjhbs.hupe.uerj.br/bjhbs/article/view/22

Copyright (c) 2022 Brazilian Journal of Health and Biomedical Sciences

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Abstract

Background: Myelodysplastic syndrome (MDS) comprises a heterogeneous group of clonal hematopoietic stem cell diseases, characterized by dysplasias and apoptosis in bone marrow (BM) and cytopenias in peripheral blood. In this study, we analyzed apoptosis in MDS to verify associations with patient age, bone marrow cellularity and karyotypes and to investigate the role of apoptosis in MDS pathogenesis. Methods: Bone marrow cells were collected from 81 patients with primary MDS, of which 60 were adults and 21 children. BM cells were also collected from 10 healthy donors for bone marrow transplants, 5 adults and 5 children, as controls. The patients and controls came from public onco-hematology institutions in Rio de Janeiro. The percentage of apoptotic BM cells was assessed by flow cytometry using two combinations: annexin V-FITC/CD34PE/CD45PerCP and annexin V-FITC/CD14PE/CD45PerCP in BM cells. Cytogenetic analysis was performed by G-banding. Results: The comparison between adult and pediatric patients showed that these patients show a similar behavior with regard to apoptotic cells percentages in BM samples. Apoptosis occurs independently of BM cellularity, being more prominent in patients with hyper/normocellular BM. Patients with normal karyotypes, del(5q), del(17p) had higher apoptosis rates than patients with del(11q) and complex karyotypes. Cells committed to a differentiation program were associated with high rates of apoptosis, suggesting that apoptosis may be a consequence of inefficient hematopoiesis, such that the hematopoietic system may eliminate dysplastic cells at the beginning of the disease. Conclusions: Our results suggest that apoptosis is an important characteristic of BM cells from adult and pediatric MDS patients and may be a consequence of inefficient hematopoiesis. In addition, we suggest that apoptosis is not the main mechanism associated with hypocellular MDS, and it occurs preferentially in MDS cases of hyper/normocellular BM and is associated with a good prognosis.

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References

  1. Zimmermann KC, Bonzon C, Green DR. The machinery of programmed cell death. Pharmacol Ther 2001;92:57-70. doi: 10.1016/s0163-7258(01)00159-0
  2. Wong RSY. Apoptosis in cancer: from pathogenesis to treatment. J Exp Clin Cancer Res. 2011;30:1-14. doi: 10.1186/1756-9966-30-87
  3. Koff JL, Ramachandiran S, Bernal-Mizrachi L. A time to kill: targeting apoptosis in cancer. Int J Mol Sci. 2015;16:2942-55. doi: 10.3390/ijms16022942
  4. Yoshida Y. A new look at apoptosis in MDS; an uneasy neighbor. Leuk Res 2007; 31:1617-19. doi: 10.1016/j.leukres.2007.06.003
  5. Invernizzi R. The role of apoptosis in myelodysplastic syndrome. Haematologica. 2002;87:337-339.
  6. Candelaria M, Dueñas-Gonzalez A. Therapy-related myelodysplastic syndrome. Expert Opin Drug Saf. 2015;12:1-11. doi: 10.1517/14740338.2015.1014340
  7. Corey SJ, Minden MD, Barber DL, et al. Myelodysplastic syndromes: the complexity of stem-cell diseases. Nat Rev Cancer. 2007;7:118-29. doi: 10.1038/nrc2047
  8. Boudard D, Vasselon C, Berthéas MF, et al. Expression and prognostic significance of Bcl-2 family proteins in myelodysplastic syndromes. Am J Hematol. 2002;70:115-25. doi: 10.1002/ajh.10108
  9. Parker JE, Mufti GJ, Rasool F, et al. The role of apoptosis, proliferation, and the Bcl-2-related proteins in the myelodysplastic syndromes and acute myeloid leukemia secondary to MDS. Blood. 2000;96:3932-3938. doi: 10.1182/blood.V96.12.3932
  10. List AF. New approaches to the treatment of myelodysplasia. Oncologist. 2002;7(Suppl 1):39-49. doi: 10.1634/theoncologist.7-suppl_1-39
  11. Pleyer L, Valent P, Greil R. Mesenchymal Stem and Progenitor Cells in normal and dysplastic hematopoiesis-masters of survvival and clonality? Int J Mol Sci. 2016;17(7):1009. doi: 10.3390/ijms17071009
  12. Niemeyer CM, Baumann I. Myelodysplastic Syndrome in Children and Adolescents. Semin Hematol. 2008;45:60-70. doi: 10.1053/j.seminhematol.2007.10.006
  13. Elghetany MT. Myelodysplastic Syndromes in Children: A Critical Review of Issues in the Diagnosis and Classification of 887 Cases from 13 Published Series. Arch Pathol Lab Med. 2007;131:1110-1116. doi: 10.5858/2007-131-1110-MSICAC
  14. Polychronopoulou S, Panagiotou JP, Kossiva L, et al. Clinical and morphological features of paediatric myelodysplastic syndromes: a review of 34 cases. Acta Paediatric. 2004;93:1015-1023. doi: 10.1111/j.1651-2227.2004.tb02708.x
  15. Tuzuner N, Cox C, Rowe JM, et al. Hypocellular myelodysplastic syndromes (MDS): new proposals. Br J Haematol.1995;91:612-617. doi: 10.1111/j.1365-2141.1995.tb05356.x
  16. Tomonaga M, Nagai K. Hypocellular Myelodysplastic Syndromes and Hypocellular Acute Myeloid Leukemia: Relationship to Aplastic Anemia. In: The Myelodysplastic Syndromes: Pathobiology and Clinical management, USA: Marcel Dekker Inc;2002. p.121-138
  17. Yue G, Hao S, Fadare O, et al. Hypocellularity in myelodysplastic syndrome is an independent factor which predicts a favorable outcome. Leuk Res. 2008;32:553-58. doi: 10.1016/j.leukres.2007.08.006
  18. Goyal R, Qawi H, Ali I, et al. Biologic characteristics of patients with hypocellular myelodysplstic syndromes. Leuk Res. 1999;23:357-364. doi: 10.1016/s0145-2126(98)00187-8
  19. de Souza DC, Fernandez CS, Camargo A, et al. Cytogenetic as an important tool for diagnosis and prognosis for patients syndrome. Biomed Res Int. 2014;2014:542395. doi: 10.1155/2014/542395
  20. Washington LT, Jilani I, Estey E, et al. Less apoptosis in patients with 5q-syndrome than in patients with refractory anemia. Leuk Res. 2002;26: 899-902. doi: 10.1016/s0145-2126(02)00039-5
  21. Sloand EM, Pfannes L, Chen G, et al. CD34 cells from patients with trisomy 8 myelodysplastic syndrome (MDS) express early apoptotic markers but avoid programmed cell death by up-regulation of antiapoptotic proteins. Blood. 2007;109:2399-2405. doi: 10.1182/blood-2006-01-030643
  22. Hasle H, Niemeyer CM, Chessels JM, et al. A pediatric approach to the WHO classification of myelodysplastic and myeloproliferative diseases. Leukemia. 2003;17:277-282. doi: 10.1038/sj.leu.2402765
  23. Bennett JM, Catovsky D, Daniel MT, et al. Proposals for the Classification of the Myelodysplastic Syndrome. Br J Haematol. 1982;51:189-199. doi: 10.1111/j.1365-2141.1982.tb02771.x
  24. Thiele J, Kvasnicka HM, Facchetti F, et al. European consensus on grading bone marrow fibrosis and assessment of cellularity. Haematologica. 2005;90:1128–32.
  25. Proytcheva M. Bone marrow evaluation for pediatric patients. International Journal of Laboratory Hematology. 2013;35: 283-289. doi: 10.1111/ijlh.12073
  26. Foucar K. Bone Marrow Pathology. 2nd ed. ASCP Press, Chicago. 2001
  27. McGowan-Jordan J, Simons A, Schmid M, editors. ISCN 2016: an international system for human cytogenetic nomenclature. Basel: Kager; 2016.
  28. Raza A, Mundle S, Shetty V, et al. Novel insights into the biology of myelodysplastic syndromes: excessive apoptosis and the role of cytokines. Int J Hematol. 1996;63:265-278. doi: 10.1016/0925-5710(96)00455-0
  29. Ogata K. Myelodysplastic syndromes: recent progress in diagnosis and understanding of their pathophysiology. J Nippon Med Sch. 2006;73:300-307. doi: 10.1272/jnms.73.300
  30. Tormo, M., Marugán, I. & Calabuig, M. Myelodysplastic syndromes: an update on molecular pathology. Clin Transl Oncol. 2010;12:652-661. doi: 10.1007/s12094-010-0574-9
  31. Davis RE, Greenberg PL. Bcl-2 expression by myeloid precursors in myelodysplastic syndromes: relation to disease progression. Leuk Res. 1998;22:767-777. doi: 10.1016/s0145-2126(98)00051-4
  32. Raza A, Galili N. The genetic basis of phenotypic heterogeneneity in myelodysplastic syndromes. Nat Rev Cancer. 2012;12:849-59. doi: 10.1038/nrc3321
  33. Serio B, Risitano AM, Giudice V, et al. Immunological Derangement in Hypocellular Myelodysplastic Syndromes. Transl Med UniSa. 2014;8:31-42.
  34. Parcharidou A, Raza A, Economopoulos T, et al. Extensive apoptosis of bone marrow cells as evaluated by the in situ end-labelling (ISEL) technique may be the basis for ineffective haematopoiesis in patients with myelodysplastic syndromes. Eur J Haematol. 1999;62:19-26. doi: 10.1111/j.1600-0609.1999.tb01109.x
  35. Boudard D, Sordet O, Vasselon C, et al. Expression and activity of caspases 1 and 3 in myelodysplastic syndromes. Leukemia. 2000;14:2045-2051. doi: 10.1038/sj.leu.2401959
  36. Yoshida Y, Anzai N, Kawabata H. Apoptosis in myelodysplasia: a paradox or paradigm. Leuk Res. 1995;19: 887-891. doi: 10.1016/0145-2126(95)00100-x
  37. Parker JE, Fishlock KL, Mijovic A, et al. “Low-risk” myelodysplastic syndrome is associated with excessive apoptosis and an increased ratio of pro-versus anti-apoptotic bcl-2-related proteins. Br J Haematol. 1998;103:1075-82. doi: 10.1046/j.1365-2141.1998.01114.x