Abstract:
: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.
journal_name
Haematologicajournal_title
Haematologicaauthors
Silva A,Jotta PY,Silveira AB,Ribeiro D,Brandalise SR,Yunes JA,Barata JTdoi
10.3324/haematol.2009.011999subject
Has Abstractpub_date
2010-04-01 00:00:00pages
674-8issue
4eissn
0390-6078issn
1592-8721pii
haematol.2009.011999journal_volume
95pub_type
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