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| Status |
Public on Feb 27, 2012 |
| Title |
GSK-3A and GSK-3B knockdown in AML cell lines |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by array
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| Summary |
Gene expression data from AML cell lines, MOLM-14, U937, THP-1 and HL-60, that were infected with a scrambled control hairpin (shControl), two shRNAs directed against GSK-3B (shGSK3B_1 and shGSK3B_2), or two shRNAs directed against GSK-3A (shGSK3A_5 and shGSK3A_6).
Acute myeloid leukemia (AML) is the most common form of acute leukemia in adults. Long-term survival of patients with AML has changed little over the past decade, necessitating the identification and validation of new AML targets. Integration of genomic approaches with small-molecule and genetic-based high-throughput screening holds the promise of improved discovery of candidate targets for cancer therapy. Here, we identified a role for glycogen synthase kinase 3A (GSK-3A) in AML by performing two independent small-molecule library screens and an shRNA screen for perturbations that induced a differentiation expression signature in AML cells. GSK-3 is a serine-threonine kinase involved in diverse cellular processes including differentiation, signal transduction, cell cycle regulation, and proliferation. We demonstrated that specific loss of GSK-3A induced differentiation in AML by multiple measurements, including induction of gene expression signatures, morphological changes, and cell surface markers consistent with myeloid maturation. GSK-3A–specific suppression also led to impaired growth and proliferation in vitro, induction of apoptosis, loss of colony formation in methylcellulose, and anti-AML activity in vivo. Although the role of GSK-3B has been well studied in cancer development, these studies support a role for GSK-3A in AML.
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| Overall design |
The AML cell lines, MOLM-14, U937, THP-1 and HL-60, were infected with a scrambled control hairpin (shControl), two shRNAs directed against GSK-3B (shGSK3B_1 and shGSK3B_2), and two shRNAs directed against GSK-3A (shGSK3A_5 and shGSK3A_6).
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| Contributor(s) |
Stegmaier K, Banerji V, Frumm SM, Ross KN |
| Citation(s) |
22326953 |
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| Submission date |
Jan 18, 2012 |
| Last update date |
Jan 17, 2017 |
| Contact name |
Kimberly Stegmaier |
| E-mail(s) |
kimberly_stegmaier@dfci.harvard.edu
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| URL |
http://www.broad.mit.edu/cancer/
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| Organization name |
Dana-Farber Cancer Institute and Children’s Hospital Boston
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| Department |
Department of Pediatric Oncology
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| Street address |
Harvard Medical School
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| City |
Boston |
| State/province |
MA |
| ZIP/Postal code |
02115 |
| Country |
USA |
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| Platforms (1) |
| GPL3921 |
[HT_HG-U133A] Affymetrix HT Human Genome U133A Array |
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| Samples (44)
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| Relations |
| BioProject |
PRJNA150689 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE35200_RAW.tar |
98.8 Mb |
(http)(custom) |
TAR (of CEL) |
| Processed data included within Sample table |
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