GEO DataSets

(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) Diagnostic samples of peripheral blood form acute myeloid leukemia were analysed for gene expression differences MLL Munich Leukemia Laboratory

Organism:

Homo sapiens

Type:

Expression profiling by array

Platform:

GPL570

325 Samples

Download data: CEL, PDF

(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) FLT3ITD are common mutations in Acute Myeloid Leukemia (AML) and carry a particularly bad prognosis. Although new generation FLT3 tyrosine kinase inhibitors (TKI) have shown promising results, the outcome of FLT3-mutated AML patients remains poor and demands the identification of novel, specific and validated therapeutic targets for this highly aggressive AML subtype. Utilizing an unbiased genome-wide CRISPR/Cas9 screen, we identify GLS, the first enzyme in glutamine metabolism, as synthetically lethal with FLT3 TKI treatment. more...

Organism:

Homo sapiens

Type:

Expression profiling by high throughput sequencing

Platform:

GPL20301

12 Samples

Download data: BW

(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) The FLT3-ITD mutation is associated with poor prognosis in acute myeloid leukemia (AML). FLT3 tyrosine kinase inhibitors (TKIs) demonstrate clinical efficacy but fail to target leukemia stem cells (LSC) and do not generate sustained responses. Autophagy is an important cellular stress response contributing to hematopoietic stem cells (HSC) maintenance and promoting leukemia development. Here we investigated the role of autophagy in regulating FLT3-ITD AML stem cell function and response to TKI treatment. more...

Organism:

Mus musculus

Type:

Expression profiling by high throughput sequencing

Platform:

GPL24247

32 Samples

Download data: XLSX

(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) To understand the mechanisms of drug resistance to AC220, we undertook an unbiased approach with a novel CRISPR pooled library to screen new genes whose loss of function confers resistance to AC220. In our screen, we identified SPRY3, an intracellular inhibitor of FGF signaling, and GSK3, a canonical Wnt signaling antagonist, and demonstrated that re-activation of downstream FGF/Ras/ERK and Wnt signaling as major mechanisms of resistance to the FLT3 inhibitor. more...

Organism:

Homo sapiens

Type:

Other

Platform:

GPL11154

1 Sample

Download data: TXT

(Submitter supplied) Utilizing genome wide transcriptome analysis and drug screen we demonstrate that upregulation of inflammatory pathways is a key mechanism of drug tolerance to FLT3 targeted inhibitors in AML

Organism:

Homo sapiens

Type:

Expression profiling by high throughput sequencing

Platform:

GPL16791

26 Samples

Download data: XLSX

(Submitter supplied) RNA-seq was used to demonstrate the differential expression genes in MOLM14 and MV4-11 cells after FLT3 inhibition.

Organism:

Homo sapiens

Type:

Expression profiling by high throughput sequencing

Platforms:

GPL18573 GPL24676

24 Samples

Download data: CSV

(Submitter supplied) The interaction of Menin (MEN1) and MLL (MLL1, KMT2A) is a dependency and potential therapeutic opportunity against NPM1 mutant (NPM1mut) and MLL-rearranged (MLL-r) leukemias. Concomitant activating driver mutations in the gene encoding the tyrosine kinase FLT3 occur in both leukemias and are particularly common in the NPM1mut subtype. Transcriptional profiling upon pharmacological inhibition of the Menin-MLL complex revealed specific changes in gene expression with downregulation of the MEIS1 transcription factor and its transcriptional target gene FLT3 being most pronounced. more...

Organism:

Homo sapiens

Type:

Expression profiling by high throughput sequencing

Platform:

GPL20301

24 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) Patients relapsing with FLT3-ITD mutant acute myeloid leukemia (AML) after allogeneic hematopoietic cell transplantation (allo-HCT) have a one-year-survival below 20%. We observed that sorafenib increased IL-15 production by FLT3-ITD+-leukemia cells, which synergized with the allogeneic CD8+T-cell response, leading to long-term survival in murine and humanized FLT3-ITD+AML models. Using IL-15 deficiency in recipient tissues or leukemia cells, IL-15 production upon sorafenib-treatment could be attributed to leukemia cells. more...

Organism:

Homo sapiens

Type:

Expression profiling by array

Platform:

GPL23159

16 Samples

Download data: CEL

(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) Cooperative dependencies between mutant oncoproteins and wild-type proteins are critical in cancer pathogenesis and therapy resistance. Although spleen tyrosine kinase (SYK) has been implicated in hematologic malignancies, it is rarely mutated. We used kinase activity profiling to identify collaborators of SYK in acute myeloid leukemia (AML) and determined that FMS-like tyrosine kinase 3 (FLT3) is transactivated by SYK via direct binding. more...

Organism:

Homo sapiens

Type:

Expression profiling by array

Platform:

GPL3921

21 Samples

Download data: CEL

(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) 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) Although chemotherapy can successfully induce remission in FLT3/ITD positive acute myeloid leukemia (AML) patients, many, especially those with a high ratio of the FLT3/ITD versus wild type allele (FLT3-AR), exhibit a high relapse rate, requiring hematopoietic stem cell (HSC) transplantation to increase the chance of long-term remission. As the bone marrow tumor microenvironment (TME) has been implicated in drug resistance, we reasoned that AML-TME interactions might be critical for leukemic precursor survival and drug resistance, and that targeting AML-TME interactions might be crucial to improving survival in FLT3/ITD AML patients. more...

Organism:

Homo sapiens

Type:

Expression profiling by high throughput sequencing

Platform:

GPL16791

7 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