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GSE33892
Homo sapiens
11 Downloadable Samples
Affymetrix Human Genome U133A 2.0 Array (hgu133a2)
Description
Gene regulatory networks that govern hematopoietic stem cells (HSC) and leukemiainitiating cells (L-IC) are deeply entangled. Thus, the discovery of compounds that target L-IC while sparing HSC is an attractive but difficult endeavor. Presently, most drug discovery approaches fail to counter-screen compounds against normal hematopoietic stem/progenitor cells (HSPC) to assess therapeutic index. Here, we present a combined in vitro and in vivo strategy to identify compounds specific to L-IC in acute myeloid leukemia (AML). A high-throughput screen of 4000 compounds on novel leukemia cell lines derived from human experimental leukemogenesis models yielded 80 hits, of which most were toxic to normal HSPC. Of the 10 compounds that passed this initial filter, we chose to characterize a single compound, kinetic riboside (KR), on AML L-IC and HSPC. KR demonstrated comparable efficacy to standard therapies against 63 primary AMLs. In vitro, KR effectively targeted the L-IC-enriched CD34+CD38- AML fraction, while sparing normal HSPC enriched fractions, although these effects were mitigated on HSC assayed in vivo, and highlights the importance of in vivo L-IC and HSC assays to measure function. Overall, we provide a novel approach to screen large drug libraries for the discovery of anti-L-IC compounds for human leukemias.
Publication Title
A small molecule screening strategy with validation on human leukemia stem cells uncovers the therapeutic efficacy of kinetin riboside.
Sample Metadata Fields
Cell line, Treatment
View Samples- Mus musculus
- 9 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
This study revealed pathogenic role of pre-BCR-independent SYK activation in high-risk B-ALL.
Publication Title
Therapeutic potential of spleen tyrosine kinase inhibition for treating high-risk precursor B cell acute lymphoblastic leukemia.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 16 Downloadable Samples
- Illumina HumanHT-12 V4.0 expression beadchip
Description
Analysis of lineage depleted human cord blood cells sequentially transduced with retro- (BCR-ABL1) and lentiviral (Ik6) vectors and the corresponding controls. Results provide important informations on the collaboration of BCR-ABL1 and Ik6 in human hematopoietic cells.
Publication Title
Dominant-negative Ikaros cooperates with BCR-ABL1 to induce human acute myeloid leukemia in xenografts.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 5 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Transcriptional profiling of human acute myelogenous leukemia (AML) CD34+ cells treated with 5 M fenretinide. Two timepoints included are 6h, 12h, covering the apoptosis-induction time window of AML CD34+ cells responsing to the fenretinide treatment. We studied gene expression series in human AML CD34+ cells with or without 5 M fenretinide treatment by cDNA microarray analysis. Several signal transduction pathways are involve, including stress response, NF-kappaB inhibition and p53 inhibition (p<0.05). These findings indicate fenretinide may represent a promising candidate for targeting AML-initiating cells.
Publication Title
Preferential eradication of acute myelogenous leukemia stem cells by fenretinide.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 3 Downloadable Samples
NextSeq 500
Description
Acute myeloid leukemia (AML) is a complex, heterogeneous disease with variable outcomes following curative intent chemotherapy. AML with inv(3) is a genetic subgroup characterized by low response rate to induction type chemotherapy and hence is among the worst long term survivorship of the AMLs. Here, we present RNA-Seq transcriptome data from OCI-AML-20, a new AML cell line with inv(3) and deletion of chromosome 7. Overall design: RNA-Seq transcriptome analysis of OCI-AML-20 cell line with three biological replicates.
Publication Title
Characterization of inv(3) cell line OCI-AML-20 with stroma-dependent CD34 expression.
Sample Metadata Fields
Disease, Cell line, Subject
View Samples- Homo sapiens
- 3 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
PML-RARa contributes to the development of APL through repression of genes important in myeloid development. Through a global approach, we have identified 2,979 high quality PML-RARa binding sites in ZnSO4 induced PR9 cells. By integration the gene expression data, we found that PML/RARa target genes are transcriptionally suppressed in primary APL cells and re-activated in ATRA treated NB4 cells.
Publication Title
PML/RARalpha targets promoter regions containing PU.1 consensus and RARE half sites in acute promyelocytic leukemia.
Sample Metadata Fields
Cell line, Treatment, Time
View Samples- Homo sapiens
- 3 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
NB4 is an APL derived cell line, carrying the t(15;17) translocation and expressing the PML/RARa fusion protein. Still, an important question that remains to be addressed is whether PML/RARa target genes are transcriptionally suppressed in primary APL cells and re-activated in all-trans retinoic acid (ATRA) treated NB4 cells. Gene expression of NB4 cells treated with ATRA at different time points were analyzed.
Publication Title
PML/RARalpha targets promoter regions containing PU.1 consensus and RARE half sites in acute promyelocytic leukemia.
Sample Metadata Fields
Cell line, Treatment, Time
View Samples- Homo sapiens
- 25 Downloadable Samples
- Illumina HiSeq 2000
Description
Transcriptome sequencing of Chronic Phase and Blast Crisis CML, normal cord blood cells, and normal cord blood cells transduced with lentiviral vectors
Publication Title
ADAR1 promotes malignant progenitor reprogramming in chronic myeloid leukemia.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 9 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Role of SWI/SNF in acute leukemia maintenance and enhancer-mediated Myc regulation.
Sample Metadata Fields
Specimen part, Cell line, Treatment
View Samples- Mus musculus
- 21 Downloadable Samples
- IlluminaHiSeq2000
Description
Cancer cells frequently depend on chromatin regulatory activities to maintain a malignant phenotype. Here, we show that leukemia cells require the mammalian SWI/SNF chromatin remodeling complex for their survival and aberrant self-renewal potential. While Brg1, an ATPase subunit of SWI/SNF, is known to suppress tumor formation in several cancer types, we found that leukemia cells instead rely on Brg1 to support their oncogenic transcriptional program, which includes Myc as one of its key targets. To account for this context-specific function, we identify a cluster of lineage-specific enhancers located 1.7 megabases downstream of Myc that are occupied by SWI/SNF, as well as the BET protein Brd4. Brg1 is required at these distal elements to maintain transcription factor occupancy and for long-range chromatin looping interactions with the Myc promoter. Notably, these distal Myc enhancers coincide with a region that is focally amplified in 3% of acute myeloid leukemia. Together, these findings define a leukemia maintenance function for SWI/SNF that is linked to enhancer-mediated gene regulation, providing general insights into how cancer cells exploit transcriptional coactivators to maintain oncogenic gene expression programs Overall design: To profile the basal transcription level, we performed NSR and PolyA+ (illumine TruSeq) in a murine AML RN2 cell lines. To define the rapid downregulated genes in response to JQ1, BET bromodomian inhibitor, in RN2 cell, we performed RNA-seq in RN2 exposing to 250nM JQ1 for 48h time course.
Publication Title
Role of SWI/SNF in acute leukemia maintenance and enhancer-mediated Myc regulation.
Sample Metadata Fields
No sample metadata fields
View Samples