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| Status |
Public on Aug 01, 2012 |
| Title |
MondoA is highly expressed in acute lymphoblastic leukemia and modulates metabolism, differentiation and survival |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by array
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| Summary |
Acute lymphoblastic leukemia (ALL) is the most common childhood cancer. To identify novel candidates for targeted treatment of childhood ALL, we performed a comprehensive transcriptome analysis yielding a set of genes specifically overexpressed in ALL. Among them we identified MondoA - a transcription factor regulating glycolysis in response to glucose availability. Here, we confirm that MondoA is highly overexpressed ALL, whereas the MondoA paralog, MondoB, is not expressed. Expression studies revealed that MondoA is not regulated by glucose availability in leukemia cells, but by the presence of lactate. An in silico MondoA promoter analysis identified two methylation-prone CpG-islands and four conserved binding sites for runt-related transcription factor 1 (RUNX1). In fact, MondoA and RUNX1 are significantly coexpressed in leukemia and experimental blockage of DNA methylation leads to a further induction of MondoA. In addition, using microarray profiling, gene-set enrichment analysis and RNA interference we provide for the first time evidence that MondoA expression not only increases glucose catabolism, but also maintains a more immature ALL phenotype, which is associated with enhanced survival and clonogenicity of leukemia cells. These data hint to an important contribution of MondoA to leukemia aggressiveness validating MondoA as an attractive candidate for targeted treatment of ALL.
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| Overall design |
Two nonsense shRNA expressing control Nalm6 clones and three MondoA shRNA expressing Nalm6 clones were subjected to microarray analysis.
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| Contributor(s) |
Wernicke CM, Grunewald TG, Richter GH, Prazeres da Costa O, Burdach S |
| Citation(s) |
22748921 |
| Submission date |
Nov 28, 2011 |
| Last update date |
Jul 26, 2018 |
| Contact name |
Olivia Prazeres da Costa |
| E-mail(s) |
olivia.p.dacosta@googlemail.com
|
| Phone |
00498941404149
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| Organization name |
Technische Universität München
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| Department |
Medical Microbiology, Immunology and Hygiene
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| Street address |
Trogerstr. 30
|
| City |
München |
| State/province |
Bavaria |
| ZIP/Postal code |
81675 |
| Country |
Germany |
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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 (5)
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| Relations |
| BioProject |
PRJNA150519 |
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