Leukemia research · 2013
The expression of histone deacetylase 4 is associated with prednisone poor-response in childhood acute lymphoblastic leukemia.
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Gruhn Bernd, Naumann Thomas, Gruner Dorothee, Walther Mario, Wittig Susan, Becker Sabine, Beck James F, Sonnemann Jürgen
Аннотация
This study aimed at the identification of histone deacetylase (HDAC) isoforms relevant for childhood acute lymphoblastic leukemia (ALL). Expression of HDAC1-11 was determined in 93 primary ALL and eight healthy donor samples. HDAC1, HDAC2 and HDAC8 showed significantly higher expressions in ALL samples. Correlation analysis of HDAC expression with clinicopathological parameters revealed that high HDAC1, HDAC2, HDAC4 and HDAC11 levels were significantly associated with unfavorable prognostic factors. Particularly, high HDAC4 expression was associated with high initial leukocyte count, T cell ALL and prednisone poor-response. siRNA-mediated inhibition of HDAC4 sensitized a T-ALL cell line to etoposide-induced cell death. In conclusion, our data point to HDAC4 as drug target in childhood ALL, especially in prednisone poor-responders.
Предметные рубрики MeSH
AdolescentAntineoplastic AgentsAntineoplastic Combined Chemotherapy ProtocolsCell Line, TumorChildChild, PreschoolFemaleGene ExpressionGene Knockdown TechniquesHistone DeacetylasesHumansInfantIsoenzymesMalePrecursor Cell Lymphoblastic Leukemia-LymphomaPrednisoneRepressor ProteinsTreatment OutcomeYoung Adult