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Title: Cytogenetic effect of 5-azacytidine in patients with hematological malignancies
Authors: Tsuda, Jessica Romy [UNIFESP]
Segato, Rosimeire [UNIFESP]
Barbosa, Waldênia
Smith, Marilia de Arruda Cardoso [UNIFESP]
Payão, Spencer Luiz Marques [UNIFESP]
Faculdade de Medicina de Marília Hemocentro Genetics Laboratory
Universidade Federal de São Paulo (UNIFESP)
Faculdade de Medicina de Marília Hematology Department
Universidade do Sagrado Coração
Keywords: Cytogenetics
Issue Date: 1-Oct-2011
Publisher: Associação Brasileira de Hematologia e Hemoterapia e Terapia Celular
Citation: Revista Brasileira de Hematologia e Hemoterapia. Associação Brasileira de Hematologia e Hemoterapia e Terapia Celular, v. 33, n. 5, p. 372-376, 2011.
Abstract: BACKGROUND: Recently, the importance of cytogenetics has grown in the diagnosis, prognosis and treatment of leukemias and myelodysplastic syndromes. 5-azacytidine is a drug that has well-known cytogenetical effects and is approved in the treatment of myelodysplastic syndromes. To date, no studies have been performed to evaluate the impact of 5-azacytidine on the chromosomes of patients with hematological neoplasias. This study aimed to investigate the effects of 5-azacytidine on chromosomes of patients with different hematological malignancies using G-band analyses to identify possible cytogenetical alterations. METHODS: The peripheral blood of 18 patients with hematological malignancies and 18 controls was collected in heparinized tubes. 5-azacytidine was added, at a final concentration of 10-5M, to cultures 7 hours prior to harvest. RESULTS: Uncoiled centromeric/pericentromeric heterochromatin of chromosomes-1, 9 and 16 occurred more frequently in the patients than in controls. This higher frequency of uncoiled heterochromatin was statistically significant (p-value = 0.004) for chromosome-9. Conversely, we observed that the fragile site at 19q13 was more frequent in controls (p-value = 0.0468). CONCLUSIONS: The results of this study suggest that satellite sequences, located in the heterochromatin of chromosome-9, are hypomethylated in hematological malignancies. This hypomethylation may contribute to the disease, activating transposable elements and/or promoting genomic instability, enabling the loss of heterozygosity of important tumor suppressor genes. An investigation of the 19q13 region may help to understand whether or not the predominant occurrence of the fragile site at 19q13 in controls is due to hypermethylation of this region.
ISSN: 1516-8484
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