Artículos de revistas
Regulation Of Pten By Ck2 And Notch1 In Primary T-cell Acute Lymphoblastic Leukemia: Rationale For Combined Use Of Ck2- And γ-secretase Inhibitors
Registro en:
Haematologica. , v. 95, n. 4, p. 674 - 678, 2010.
3906078
10.3324/haematol.2009.011999
2-s2.0-77950668038
Autor
Silva A.
Jotta P.Y.
Silveira A.B.
Ribeiro D.
Brandalise S.R.
Yunes J.A.
Barata J.T.
Institución
Resumen
T-cell acute lymphoblastic leukemia (T-ALL) patients frequently display NOTCH1 activating mutations and Notch can transcriptionally down-regulate the tumor suppressor PTEN. However, it is not clear whether NOTCH1 mutations associate with decreased PTEN expression in primary T-ALL. Here, we compared patients with or without NOTCH1 mutations and report that the former presented higher MYC transcript levels and decreased PTEN mRNA expression. We recently showed that T-ALL cells frequently display CK2-mediated PTEN phosphorylation, resulting in PTEN protein stabilization and concomitant functional inactivation. Accordingly, the T-ALL samples analyzed, irrespectively of their NOTCH1 mutational status, expressed significantly higher PTEN protein levels than normal controls. To evaluate the integrated functional impact of Notch transcriptional and CK2 post-translational inactivation of PTEN, we treated T-ALL cells with both the gamma-secretase inhibitor DAPT and the CK2 inhibitors DRB/TBB. Our data suggest that combined use of gamma-secretase and CK2 inhibitors may have therapeutic potential in T-ALL. © 2010 Ferrata Storti Foundation. 95 4 674 678 Weng, A.P., Ferrando, A.A., Lee, W., Morris JPt, Silverman LB, Sanchez-Irizarry C, et al. 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