Abstract | BACKGROUND: METHODS: We examined the expression levels of PRC2 complex in primary samples of T cells ALL at diagnosis by western blotting and real time PCR. We evaluated the effect of 3-deazaneplanocin-A ( DZNep), an EZH2 inhibitor, alone and in combination with Daunoblastine on cell viability, apoptotic death and cell cycle distribution of T cell established Jurkat cell line. RESULTS: EZH2 was expressed in 75 % samples at different extents mainly with high expression level. SUZ12 was expressed in 60 % samples and EED in all samples, respectively. The Kaplan-Meier analysis shows that T-ALL expressing EZH2 had a lower probability of disease-free survival (DFS) compared to T-ALL negative for EZH2 (23 % vs 100 %) (p = 0.01). The EZH2 inhibitor DZNep used in combination with Daunoblastine was synergistic in inducing growth inhibition and increasing the apoptosis in T-ALL Jurkat cells at 48 and 72 h paralleled by EZH2 decreased expression. Moreover, the combination decreased the activity of Erk-1/2 proliferation enzymes with no effects on Akt survival pathway. CONCLUSIONS: The evaluation of EZH2 expression in pediatric T-ALL can be useful in predict the clinical outcome of the patients and EZH2 can be a useful target to improve the efficacy of conventional chemotherapy in this subset of patients with bad prognosis.
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Authors | V D'Angelo, A Iannotta, M Ramaglia, A Lombardi, M R Zarone, V Desiderio, M C Affinita, G Pecoraro, M Di Martino, P Indolfi, F Casale, M Caraglia |
Journal | Journal of experimental & clinical cancer research : CR
(J Exp Clin Cancer Res)
Vol. 34
Pg. 83
(Aug 14 2015)
ISSN: 1756-9966 [Electronic] England |
PMID | 26268310
(Publication Type: Journal Article)
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Chemical References |
- EZH2 protein, human
- Enhancer of Zeste Homolog 2 Protein
- Polycomb Repressive Complex 2
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Topics |
- Cell Line, Tumor
- Cell Proliferation
- Child
- Enhancer of Zeste Homolog 2 Protein
- Epigenesis, Genetic
(genetics)
- Female
- Gene Expression
(genetics)
- Humans
- Male
- Polycomb Repressive Complex 2
(genetics, metabolism)
- Precursor T-Cell Lymphoblastic Leukemia-Lymphoma
(genetics, therapy)
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