GEO DataSets

(Submitter supplied) Fms-like tyrosine kinase 3 (FLT3) is a critical receptor for functional dendritic cell (DC) development. Mutations associated with FLT3 are commonly observed in acute myeloid leukemia (AML) patients. Internal tandem duplication (FLT3-ITD) results in ligand-independent constitutive signaling and promotes tumor survival. Basic characterization of dendritic cells in the context of AML is lacking, therefore we investigated how FLT3-ITD impacts DC homeostasis and what downstream affects on the immune system may be. more...

Organism:

Mus musculus

Type:

Expression profiling by high throughput sequencing

Platform:

GPL21103

16 Samples

Download data: MTX, TSV

(Submitter supplied) One of the most common genetic alterations in acute myeloid leukemia is the internal tandem duplication (ITD) in the FLT3 receptor for cytokine FLT3 ligand (FLT3L). The constitutively active FLT3-ITD promotes the expansion of transformed progenitors, but also has pleiotropic effects on normal hematopoiesis. We analyzed the effect of FLT3-ITD on dendritic cells (DCs), which express FLT3 and can be expanded by FLT3L administration. more...

Organism:

Mus musculus

Type:

Expression profiling by high throughput sequencing

Platform:

GPL17021

24 Samples

Download data: CSV

(Submitter supplied) Internal tandem duplication (ITD) mutations within the FMS-like receptor tyrosine kinase-3 (FLT3) can be found in up to 25~30% of acute myeloid leukemia (AML) patients and confer a poor prognosis. Although FLT3 tyrosine kinase inhibitors (TKIs) have shown clinical responses, the overall outcome of FLT3-ITD+ AML patients remains poor, and most of them would relapse very shortly. TKIs can not eliminate primitive FLT3-ITD+ AML cells, which are potential sources of relapse. more...

Organism:

Homo sapiens

Type:

Expression profiling by high throughput sequencing

Platform:

GPL20301

6 Samples

Download data: TXT

(Submitter supplied) we observed synergistic cytotoxic effects, preferentially reducing cell proliferation and inducing apoptosis in FLT3/ITD+ AML cell lines and in primary AML cells. Furthermore, the combination of FLT3-TKI and GSI eradicated leukemic cells and prolonged survival in a FLT3/ITD+ patient derived xenograft (PDX) AML model. Mechanistically, decreased expression of CXCR3 that lead to down-regulated ERK signaling was partially responsible for the observed synergy. more...

Organism:

Homo sapiens

Type:

Expression profiling by high throughput sequencing

Platform:

GPL23227

16 Samples

Download data: TXT

(Submitter supplied) The miR-155-dependent differences in gene expression in the HSPC compartment of FLT3-ITD mice is unknown. In this experiment, we performed RNA sequencing on FLT3-ITD and FLT3-ITD miR-155-/- mouse LKS cells.

Organism:

Mus musculus

Type:

Expression profiling by high throughput sequencing

Platform:

GPL17021

6 Samples

Download data: TXT

(Submitter supplied) RNA-seq was used to determine the differentially expressed genes after overexpression of two human Follistatin (FST) isoforms, FST317 and FST344 in human acute myeloid leukemia cell line ML-2.

Organism:

Homo sapiens

Type:

Expression profiling by high throughput sequencing

Platform:

GPL18460

3 Samples

Download data: TXT

(Submitter supplied) CircMYBL2 is more highly expressed in AML patients with FLT3-ITD mutations than in those without the FLT3-ITD mutation. We found that circMYBL2 knockdown specifically inhibits proliferation and promotes the differentiation of FLT3-ITD AML cells in vitro and in vivo. We used the ribosome profiling and RNA-seq libraries sequenced with Illumina HiSeq 2500 to identify the mRNA that circMYBL2 targeted. Interestingly, we found that circMYBL2 significantly influences the protein level of mutant FLT3 kinase, which contributes to the activation of FLT3-ITD-dependent signaling pathways. more...

Organism:

Homo sapiens

Type:

Expression profiling by high throughput sequencing; Other

Platform:

GPL24676

8 Samples

Download data: CSV, TXT

(Submitter supplied) Different gene expression profile was observed in bone marrow Sca-1+ versus Sca-1- endothelial cells

Organism:

Mus musculus

Type:

Expression profiling by high throughput sequencing

Platform:

GPL17021

9 Samples

Download data: TXT

(Submitter supplied) Fms-like tyrosine kinase 3 (Flt3) tyrosine kinase inhibitors (Flt3-TKI) have improved outcomes for patients with Flt3-mutated acute myeloid leukemia (AML) but are limited by resistance and relapse, suggesting persistence of leukemia stem cells (LSC). Here we utilized a Flt3-internal tandem duplication (Flt3-ITD) and Tet2-deleted AML genetic mouse model to characterize Flt3-ITD AML LSC and their resistance to Flt3-TKI. more...

Organism:

Mus musculus

Type:

Expression profiling by high throughput sequencing

Platform:

GPL24247

11 Samples

Download data: TXT

(Submitter supplied) Gene expression in control and Flt3-ITD, Stat5 and Runx1 mutant HSCs and HPCs from different developmental stages.

Organism:

Mus musculus

Type:

Expression profiling by array

Platforms:

GPL21163 GPL10787

117 Samples

Download data: TXT

(Submitter supplied) Internal tandem duplications (ITD) of FLT3 predict poor prognosis in acute myeloid leukemia (AML) and often co-exist with inactivating DNMT3A mutations. In a genetically modified mouse model harboring these genetic aberrations, we analyzed the role of the adaptor protein Gab2 in this disease. We observed Gab2 to be essential for the development of Flt3-ITD driven AML in vivo, which was corroborated by RNA sequencing data of whole murine bone marrow with different Gab2 genotypes

Organism:

Mus musculus

Type:

Expression profiling by high throughput sequencing

Platform:

GPL21103

8 Samples

Download data: TXT

(Submitter supplied) Internal tandem duplication (ITD) of the fms-related tyrosine kinase-3 (FLT3) gene occurs in 30% acute myeloid leukemias (AML) and confers a poor prognosis. Thirteen relapsed or chemo-refractory FLT3-ITD+ AML patients were treated with sorafenib (200-400 mg twice daily). Twelve patients showed clearance or near clearance of bone marrow (BM) myeloblasts after 27 (range 21–84) days with evidence of differentiation of leukemia cells. more...

Organism:

Homo sapiens

Type:

Expression profiling by array

Platform:

GPL6244

8 Samples

Download data: CEL, CHP

(Submitter supplied) FLT3 is a receptor tyrosine kinase that is frequently mutated in AML. Inhibition of FLT3 induces myeloid differentiation in AML patients. We identified a role of FLT3 inhibition in decreasing EZH2 expression. To assess the impact of this regulation on PRC2 function, we performed H3K27me3 ChIP-Seq in a FLT3 mutated human AML cell line.

Organism:

Homo sapiens

Type:

Genome binding/occupancy profiling by high throughput sequencing

Platform:

GPL20301

8 Samples

Download data: BROADPEAK, BW

(Submitter supplied) The development of all dendritic cells (DCs) including antigen-presenting conventional DCs (cDCs) and cytokine-producing plasmacytoid DCs (pDCs) is controlled by the growth factor Flt3 ligand (Flt3L) and its receptor Flt3. We genetically dissected this common Flt3L-driven pathway of DCs differentiation using CRISPR/Cas9-based dropout screening in a Flt3L dependent progenitor cell line. Genome-wide screening identified multiple regulators of DC differentiation including the glycosylphosphatidylinositol transamidase complex and arginine methyltransferase Carm1, whose role was confirmed in vivo. more...

Organism:

Mus musculus

Type:

Expression profiling by high throughput sequencing

Platform:

GPL24247

4 Samples

Download data: CSV

(Submitter supplied) The development of all dendritic cells (DCs) including antigen-presenting conventional DCs (cDCs) and cytokine-producing plasmacytoid DCs (pDCs) is controlled by the growth factor Flt3 ligand (Flt3L) and its receptor Flt3. We genetically dissected this common Flt3L-driven pathway of DCs differentiation using CRISPR/Cas9-based dropout screening in a Flt3L dependent progenitor cell line. Genome-wide screening identified multiple regulators of DC differentiation including the glycosylphosphatidylinositol transamidase complex and arginine methyltransferase Carm1, whose role was confirmed in vivo. more...

Organism:

Mus musculus

Type:

Other; Third-party reanalysis

Platform:

GPL19057

5 Samples

Download data: CSV

(Submitter supplied) The development of all dendritic cells (DCs) including antigen-presenting conventional DCs (cDCs) and cytokine-producing plasmacytoid DCs (pDCs) is controlled by the growth factor Flt3 ligand (Flt3L) and its receptor Flt3. We genetically dissected this common Flt3L-driven pathway of DCs differentiation using CRISPR/Cas9-based dropout screening in a Flt3L-dependent progenitor cell line. Genome-wide screening identified multiple regulators of DC differentiation including the glycosylphosphatidylinositol transamidase complex and arginine methyltransferase Carm1, whose role was confirmed in vivo. more...

Organism:

Mus musculus; unidentified plasmid

Type:

Other

Platforms:

GPL32254 GPL21103

6 Samples

Download data: CSV

(Submitter supplied) This SuperSeries is composed of the SubSeries listed below.

Organism:

unidentified plasmid; Mus musculus

Type:

Expression profiling by high throughput sequencing; Genome binding/occupancy profiling by high throughput sequencing; Other

4 related Platforms

38 Samples

Download data: BW

(Submitter supplied) The development of all dendritic cells (DCs) including antigen-presenting conventional DCs (cDCs) and cytokine-producing plasmacytoid DCs (pDCs) is controlled by the growth factor Flt3 ligand (Flt3L) and its receptor Flt3. We genetically dissected this common Flt3L-driven pathway of DCs differentiation using CRISPR/Cas9-based dropout screening in a Flt3L-dependent progenitor cell line. Genome-wide screening identified multiple regulators of DC differentiation including the glycosylphosphatidylinositol transamidase complex and arginine methyltransferase Carm1, whose role was confirmed in vivo. more...

Organism:

Mus musculus

Type:

Expression profiling by high throughput sequencing

Platform:

GPL24247

15 Samples

Download data: BW

(Submitter supplied) The development of all dendritic cells (DCs) including antigen-presenting conventional DCs (cDCs) and cytokine-producing plasmacytoid DCs (pDCs) is controlled by the growth factor Flt3 ligand (Flt3L) and its receptor Flt3. We genetically dissected this common Flt3L-driven pathway of DCs differentiation using CRISPR/Cas9-based dropout screening in a Flt3L-dependent progenitor cell line. Genome-wide screening identified multiple regulators of DC differentiation including the glycosylphosphatidylinositol transamidase complex and arginine methyltransferase Carm1, whose role was confirmed in vivo. more...

Organism:

Mus musculus

Type:

Genome binding/occupancy profiling by high throughput sequencing

Platform:

GPL21103

8 Samples

Download data: BW

(Submitter supplied) High-dimensional approaches have revealed emerging heterogeneity within dendritic cells (DC), including a population of transitional DC (tDC) present in mouse and human. However, tDC origin and relationship to other DC subsets are not fully understood because their phenotype partially overlaps with previous definitions of conventional DC precursors (pre-cDC). Here, we show that tDC are distinct from other well-characterized DC and pre-cDC. more...

Organism:

Mus musculus

Type:

Expression profiling by array

Platform:

GPL25266

12 Samples

Download data: RCC