Differential expression of HDAC3, HDAC7 and HDAC9 is associated with prognosis and survival in childhood acute lymphoblastic leukaemia

Autor(es)

Moreno, Daniel Antunes ^[1] ; Scrideli, Carlos Alberto ^[2] ; Abdala Cortez, Maria Angelica ^[1] ; Queiroz, Rosane de Paula ^[2] ; Valera, Elvis Terci ^[2] ; Silveira, Vanessa da Silva ^[1] ; Yunes, Jose Andres ^{[3, 4]} ; Brandalise, Silvia Regina ^{[3, 4]} ; Tone, Luiz Gonzaga ^{[2, 1]}

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Dept Genet, BR-14048900 Sao Paulo - Brazil

^[2] Univ Sao Paulo, FMRP, Dept Paediat, BR-14048900 Sao Paulo - Brazil

^[3] Univ Estadual Campinas, Ctr Infantil Boldrini, Sao Paulo - Brazil

^[4] Univ Estadual Campinas, Dept Paediat, Sao Paulo - Brazil

• Tipo de documento: Artigo Científico
• Fonte: British Journal of Haematology; v. 150, n. 6, p. 665-673, SEP 2010.
• Citações Web of Science: 98

Resumo

Altered expression of histone deacetylases (HDACs) is a common feature in several human malignancies and may represent an interesting target for cancer treatment, including haematological malignancies. We evaluated the mRNA gene expression profile of 12 HDAC genes by quantitative real-time polymerase chain reaction in 94 consecutive childhood acute lymphoblastic leukaemia (ALL) samples and its association with clinical/biological features and survival. ALL samples showed higher expression levels of HDAC2, HDAC3, HDAC8, HDAC6 and HDAC7 when compared to normal bone marrow samples. HDAC1 and HDAC4 showed high expression in T-ALL and HDAC5 was highly expressed in B-lineage ALL. Higher than median expression levels of HDAC3 were associated with a significantly lower 5-year event-free survival (EFS) in the overall group of patients (P = 0.03) and in T-ALL patients (P = 0.01). HDAC7 and HADC9 expression levels higher than median were associated with a lower 5-year EFS in the overall group (P = 0.04 and P = 0.003, respectively) and in B-lineage CD10-positive patients (P = 0.009 and P = 0.005, respectively). Our data suggest that higher expression of HDAC7 and HDAC9 is associated with poor prognosis in childhood ALL and could be promising therapeutic targets for the treatment of refractory childhood ALL. (AU)

• Processo FAPESP: 02/03182-8 - Genoma clínico: avaliação dos grupos filiados
• Beneficiário: Silvia Regina Brandalise
• Modalidade de apoio: Auxílio à Pesquisa - Programa GENOMA
• Processo FAPESP: 05/50731-5 - Estudo do padrão da expressão de genes relacionados à resistência/sensibilidade aos quimioterápicos na leucemia linfóide aguda da criança e do adolescente
• Beneficiário: Luiz Gonzaga Tone
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 01/13206-9 - Padrão da expressão gênica da leucemia linfoblástica aguda da infância associada à resistência à quimioterapia
• Beneficiário: Luiz Gonzaga Tone
• Modalidade de apoio: Auxílio à Pesquisa - Programa GENOMA