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GSE111678
Homo sapiens
253 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Many cases of acute myeloid leukemia (AML) are associated with mutational activation of RTKs such as FLT3. However, RTK inhibitors have limited clinical efficacy as single agents, indicating that AML is driven by concomitant activation of different signaling molecules. We used a functional genomic approach to identify RET, encoding an RTK not previously implicated in AML, as essential gene in different AML subtypes, and observed that RET-dependent AML cells show activation of RET signaling via ARTN/GFRA3 and NRTN/GFRA2 ligand/co-receptor complexes.
Publication Title
RET-mediated autophagy suppression as targetable co-dependence in acute myeloid leukemia.
Sample Metadata Fields
Specimen part, Disease
View Samples- Homo sapiens
- 10 Downloadable Samples
- Illumina HumanHT-12 V4.0 expression beadchip
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Inhibition of the LSD1 (KDM1A) demethylase reactivates the all-trans-retinoic acid differentiation pathway in acute myeloid leukemia.
Sample Metadata Fields
Cell line, Treatment
View Samples- Homo sapiens
- 10 Downloadable Samples
- Illumina HumanHT-12 V4.0 expression beadchip
Description
All-trans-retinoic acid (ATRA) has been successfully used in therapy of acute promyelocytic leukemia (APL), a cytogenetically distinct subtype of acute myeloid leukemia (AML) but the response of non-APL AML cases to ATRA-based treatment has been poor. Here we show that, via epigenetic reprogramming, inhibitors of LSD1/KDM1 demethylase including tranylcypromine (TCP) unlocked the ATRA-driven therapeutic response in non-APL AML. LSD1 inhibition did not lead to an increase in genome-wide H3 lysine4 dimethylation (H3K4me2) but did increase H3K4me2 and expression of myeloid differentiation-associated genes. Importantly, treatment with ATRA plus TCP dramatically diminished engraftment of primary human AML cells in vivo in NOD.SCID mice, suggesting that ATRA in combination with TCP may target leukemia-initiating cells. Furthermore, initiation of ATRA plus TCP co-treatment 15 days post-engraftment of human AML cells in NOD.SCID gamma mice also revealed the ATRA plus TCP drug combination to have a potent anti-leukemic effect, which was superior to treatment with either drug alone. These data identify LSD1 as a therapeutic target and strongly suggest that it may contribute to AML pathogenesis by inhibiting the normal pro-differentiative function of ATRA, paving the way for novel combinatorial therapies of AML.
Publication Title
Inhibition of the LSD1 (KDM1A) demethylase reactivates the all-trans-retinoic acid differentiation pathway in acute myeloid leukemia.
Sample Metadata Fields
Cell line, Treatment
View Samples- Homo sapiens
- 4 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Loss of the histone methyltransferase EZH2 induces resistance to multiple drugs in acute myeloid leukemia.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Homo sapiens
- 4 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Here, we analyzed global gene expression changes that were associated with drug resistance in Acute Myeloid Leukemia using the Affymetrix microarray platform.
Publication Title
Loss of the histone methyltransferase EZH2 induces resistance to multiple drugs in acute myeloid leukemia.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Mus musculus, Homo sapiens
- 6 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
AML1-ETO requires enhanced C/D box snoRNA/RNP formation to induce self-renewal and leukaemia.
Sample Metadata Fields
Specimen part, Disease
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Microarray gene profilling indentified snoRNAs are downstream target of Amino Enhancer of Split (AES) and are essential for AML1-ETO9a induced leukemia.
Publication Title
AML1-ETO requires enhanced C/D box snoRNA/RNP formation to induce self-renewal and leukaemia.
Sample Metadata Fields
No sample metadata fields
View Samples