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| Status |
Public on Mar 29, 2012 |
| Title |
The histone demethylase KDM1A sustains the oncogenic potential of MLL-AF9 leukemia stem cells (expression data) |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by array
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| Summary |
Using a mouse model of human MLL-AF9 leukemia, we identified the lysine-specific demethylase KDM1A (LSD1 or AOF2) as an essential regulator of leukemia stem cell (LSC) potential. KDM1A acts at genomic loci bound by MLL-AF9 to sustain expression of the associated oncogenic program, thus preventing differentiation and apoptosis. In vitro and in vivo pharmacologic targeting of KDM1A using tranylcypromine analogues active in the nanomolar range phenocopied Kdm1a knockdown in both murine and primary human AML cells exhibiting MLL translocations. By contrast, the clonogenic and repopulating potential of normal hematopoietic stem and progenitor cells was spared. Our data establish KDM1A as a key effector of the differentiation block in MLL leukemia which may be selectively targeted to therapeutic effect.
To investigate the genetic program regulated by KDM1A in murine MLL-AF9 AML cells enriched for LSCs, we compared the transcriptome of KIT+Gr1+ control and Kdm1a KD cells using exon arrays soon after initiation of KD. At this time, there was no immunophenotypic evidence of differentiation in Kdm1a KD cells. Exonic expression values were condensed into gene-level expression summaries, which represent the mean expression value of the probe sets targeting the length of a given protein coding gene.
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| Overall design |
Three separate samples from two different animals were used. Kdm1a KD samples were compared with control samples. Total six arrays.
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| Contributor(s) |
Somervaille TC |
| Citation(s) |
22464800 |
| |
| Submission date |
Mar 07, 2012 |
| Last update date |
Mar 03, 2017 |
| Contact name |
Tim C Somervaille |
| E-mail(s) |
tim.somervaille@cruk.manchester.ac.uk
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| Organization name |
Cancer Research UK Manchester Institute
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| Lab |
Leukaemia Biology Laboratory
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| Street address |
Wilmslow Road
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| City |
Manchester |
| State/province |
Lancashire |
| ZIP/Postal code |
M20 4BX |
| Country |
United Kingdom |
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| Platforms (1) |
| GPL6193 |
[MoEx-1_0-st] Affymetrix Mouse Exon 1.0 ST Array [probe set (exon) version] |
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| Samples (6)
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| This SubSeries is part of SuperSeries: |
| GSE36348 |
The histone demethylase KDM1A sustains the oncogenic potential of MLL-AF9 leukemia stem cells |
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| Relations |
| BioProject |
PRJNA155567 |
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