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| Status |
Public on Apr 30, 2015 |
| Title |
Gene expression data of diagnostic childhood T-ALL samples |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by array
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| Summary |
The PI3K pathway is frequently hyperactivated in primary T-cell acute lymphoblastic leukemia (T-ALL) cells. Activation of the PI3K pathway has been suggested as one mechanism of glucocorticoid resistance in T-ALL, and patients harboring mutations in the PI3K negative regulator PTEN may be at increased risk of induction failure and relapse. In this study, we identified Myc as an important downstream integrator of PI3K pathway activity in T-ALL and we provide data supportive of an association of higher PI3K activity with glucocorticoid resistance and worse clinical outcome. The PI3K inhibitor AS605240 showed anti-leukemic activity and strong synergism with glucocorticoids both in vitro and in a NOD/SCID xenograft model of T-ALL. In contrast, PI3K inhibition showed antagonism with methotrexate and daunorubicin, drugs that preferentially target dividing cells. This antagonistic interaction, however, could be circumvented by the use of correct drug scheduling schemes. Our data indicate the potential benefits and difficulties for the incorporation of PI3K inhibitors in T-ALL therapy.
Global gene expression data of diagnostic T-ALL samples were used to analyse whether a gene expression signature of higher PI3K pathway activity is associated with worse prognosis. Patients entered treatment from 2000 to 2007 at Centro Infantil Boldrini. Risk classification and treatment was performed according to the Brazilian Childhood Cooperative Group-Protocol ALL-99.
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| Overall design |
Guanidine thiocyanate solution-preserved post-ficoll bone marrow mononuclear cells obtained from consecutive patients with newly diagnosed childhood T-ALL were analysed.
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| Contributor(s) |
Silveira AB, Laranjeira ÂB, Leal P, Cardoso BA, Barata JP, Yunes RA, Zanchin NI, Brandalise SR, Yunes JA |
| Citation(s) |
25869207, 26456771 |
| |
| Submission date |
Sep 18, 2013 |
| Last update date |
Jul 26, 2018 |
| Contact name |
Andre Bortolini Silveira |
| E-mail(s) |
[email protected]
|
| Organization name |
Institut Curie
|
| Department |
U830
|
| Lab |
DRUM team
|
| Street address |
26 rue d'Ulm
|
| City |
Paris |
| ZIP/Postal code |
75005 |
| Country |
France |
| |
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| Platforms (1) |
| GPL6244 |
[HuGene-1_0-st] Affymetrix Human Gene 1.0 ST Array [transcript (gene) version] |
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| Samples (43)
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| This SubSeries is part of SuperSeries: |
| GSE51001 |
PI3K inhibition synergizes with glucocorticoids but antagonizes with methotrexate in T-cell acute lymphoblastic leukemia. |
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| Relations |
| BioProject |
PRJNA219727 |
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