Selective inhibition of Aurora A and B kinases effectively induces cell cycle arrest in t(8;21) acute myeloid leukemia - 31/07/19
, Kailin Xu a, b, ⁎ Bienvenue sur EM-consulte, la référence des professionnels de santé.
L’accès au texte intégral de cet article nécessite un abonnement.
| pages | 8 |
| Iconographies | 5 |
| Vidéos | 0 |
| Autres | 0 |
Highlights |
• | Aurora kinase A and B inhibitors suppress the proliferation of t(8;21) AML by inducing G2/M accumulation. |
• | The t(8;21) AML cells are more sensitive to Aurora B inhibition compared with Aurora A. |
• | This study provide novel approach to t(8;21) AML target therapy. |
Abstract |
The fusion gene AML1-ETO initially dysregulates various cell cycle molecules in t(8;21) acute myeloid leukemia. Aurora kinases have shown great promise in treating tumors. However, the efficacy of Aurora kinase (AURK) A and B inhibition in t(8;21) AML remains unclear. We found that AURK-A inhibitor Alisertib and AURK-B inhibitor Barasertib strongly inhibited the growth and proliferation of t(8;21) AML cells. The quantity and size of cell colonies were markedly decreased after a 14-d drug exposure. The cell cycle distribution was blocked at the G2/M phase in both dose- and time-dependent manner. The expression of p53 family and cdc2-p34 significantly changed as well. Notably, we found that t(8;21) AML cells are more sensitive to Aurora B inhibition. In each set of experiments, Barasertib took less time or a lower concentration to achieve similar efficacy. Taken together, our data highlighted the potential role of Aurora kinases as promising cell cycle targets for the treatment of t(8;21) AML and hereby provided a theoretical basis to guide relevant clinical trials.
Le texte complet de cet article est disponible en PDF.Keywords : Aurora kinase, AML-ETO, Acute myeloid leukemia, Alisertib, Barasertib
Plan
Vol 117
Article 109113- septembre 2019 Retour au numéro
Article précédent
- An oncogenic gene, SNRPA1, regulates PIK3R1, VEGFC, MKI67, CDK1 and other genes in colorectal cancer
- Qingmin Zeng, Fuming Lei, Yigang Chang, Zhaoya Gao, Yanzhao Wang, Qingkun Gao, Pengfei Niu, Qiang Li
- Long-term anesthetic analgesic effects: Comparison of tetracaine loaded polymeric nanoparticles, solid lipid nanoparticles, and nanostructured lipid carriers in vitro and in vivo
- Xiaoli Liu, Qianqian Zhao
Bienvenue sur EM-consulte, la référence des professionnels de santé.
L’accès au texte intégral de cet article nécessite un abonnement.
Bienvenue sur EM-consulte, la référence des professionnels de santé.
L’achat d’article à l’unité est indisponible à l’heure actuelle.
Déjà abonné à cette revue ?