Estudo da expressão dos genes de classe I das histonas desacetilases (HDACs 1,2,3 e 8) em Leucemia Linfóide Aguda de crianças e adolescentes / Class 1 Histone Deacetylases Gene Expression in Childhood Acute Lymphoblastic Leukemia

AUTOR(ES)
DATA DE PUBLICAÇÃO

2008

RESUMO

Acute Lymphoblastic Leukemia (ALL) is a heterogeneous disease with distinct biologic and prognostic groups. In addition to genetic alterations, epigenetic processes play an important role in carcinogenesis, among which histone acetylation/deacetylation is crucial for chromatin modulation structure and transcriptional activity. Histone acetylation is regulated by the enzyme histone acetyl transferases (HATs). On the other hand, the deacetylation process is regulated by histone deacetylases (HDACs) enzymes, which is associated with the chromatin condensation and transcriptional repression. Abnormal expression of HDACs is a common feature of cancer and has revealed a promising field to stratify cancer treatment and risk classification. The investigation of these expression profiles may represent an important clinical factor for diagnosis and management of hematological malignances. The objectives of the present study were to analyze the expression profile of the class 1 HDACs (HDAC1, 2, 3 and 8) genes in bone marrow samples obtained from 46 childhood ALL samples, to correlate the results with prognostic and clinical features (age, gender, risk group, immunophenotype, treatment response, minimal residual disease and event free survival) of the patients; to evaluated differences in gene expression between ALL samples and 10 bone marrow samples without hematological disease and to verify the correlation of these genes. The gene expression analysis were made using xi TaqMan real-time polymerase chain reaction. A higher expression of HDAC1 in patients with better treatment response was observed. The HDAC2 showed a higher expression in male gender (p=0,038). HDAC2 also showed a higher expression for higher risk (p=0,060) and lower survival patients (p=0,065), however the statistical analysis did not show significant results. Furthermore, there was a higher expression of HDAC2 (p=0,007), HDAC3 (p=0,014) and HDAC8 (p=0,002) in ALL samples when compared to healthy donors. Class I HDACs showed correlation in gene expression, except for HDAC1 and HDAC8. These results suggest that class I HDACs can represent important targets for ALL research; however, it is necessary to perform functional investigation to confirm these results.

ASSUNTO(S)

leucemia linfóide aguda acetilação criança acetylation childhood acute lymphoblastic leukemia histones deacetylases histonas desacetilases

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