Cytogenetic effect of 5-azacytidine in patients with hematological malignancies
Rev. bras. hematol. hemoter
;
33(5): 372-376, Oct. 2011. ilus, tab
Article
Dans Anglais
| LILACS
| ID: lil-606714
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.
Texte intégral:
Disponible
Indice:
LILAS (Amériques)
Sujet Principal:
Azacitidine
/
Syndromes myélodysplasiques
/
Hétérochromatine
/
Leucémies
/
Tumeurs hématologiques
/
Analyse cytogénétique
Limites du sujet:
Femelle
/
Humains
/
Mâle
langue:
Anglais
Texte intégral:
Rev. bras. hematol. hemoter
Thème du journal:
Hématologie
Année:
2011
Type:
Article
Pays d'affiliation:
Brésil
Institution/Pays d'affiliation:
Faculdade de Medicina de Marília/BR
/
Universidade Federal de São Paulo/BR
Documents relatifs à ce sujet
MEDLINE
...
LILACS
LIS