Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

GATM-Mediated Creatine Biosynthesis Enables Maintenance of FLT3-ITD-Mutant Acute Myeloid Leukemia

ABSTRACT: RNA-seq was used to demonstrate the differential expression genes in MOLM14 and MV4-11 cells after FLT3 inhibition.

ORGANISM(S): Homo sapiens

PROVIDER: GSE181586 | GEO | 2021/09/22

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Serine biosynthesis is a metabolic vulnerability in FLT3-ITD-driven acute myeloid leukaemia [MV411_OCI-AML3_DMSO_AC220_24hr]

Project description:We performed 3'-RNA-Sequencing on RNA isolated from human MV4-11 and OCI-AML3 cells which had been treated with DMSO or the FLT3 inhibitor Quizartinib (AC220) to perform differential gene expression analysis.

2021-01-13 | GSE163930 | GEO

Serine biosynthesis is a metabolic vulnerability in FLT3-ITD-driven acute myeloid leukaemia [MV411_OCI-AML3_ATF4_RNAP2_CHIP]

Project description:We performed ChIP-seq on MV4-11 or OCI-AML3 cells which had been treated with DMSO or 5 nM of the FLT3 inhibitor Quizartinib (AC220) to determine the location of ATF4 or RNAPII across the genome.

2021-01-13 | GSE163922 | GEO

GATM-Mediated Creatine Biosynthesis Enables Maintenance of FLT3-ITD-Mutant Acute Myeloid Leukemia

Project description:GATM-Mediated Creatine Biosynthesis Enables Maintenance of FLT3-ITD-Mutant Acute Myeloid Leukemia

| PRJNA752603 | ENA

PRMT1-mediated FLT3 arginine methylation promotes FLT3-ITD+ Acute Myeloid Leukemia maintenance

Project description:We want to obtain FLT3-ITD gene signature. To do so, we transduced CB CD34+ cells with mock or FLT3-ITD vectors and performed RNA sequencing (RNA-Seq). Two Groups: Group1: CB CD34+ cells transduced with mock vector; Group2: CB CD34+ cells transduced with FLT3-ITD vector;

2020-04-01 | GSE129754 | GEO

PRMT1-mediated FLT3 arginine methylation is required for maintenance of FLT3-ITD+ Acute Myeloid Leukemia

Project description:The presence of FLT3-ITD mutations in patients with acute myeloid leukemia (AML) is associated with poor clinical outcome. FLT3 tyrosine kinase inhibitors (TKIs), although effective in kinase ablation, do not eliminate FLT3-ITD+ leukemia stem cells (LSCs) which are potential sources of disease relapse, prompting us to ask whether FLT3-ITD protein regulates the AML LSCs survival through a kinase-independent mechanism. Here, we show that expression of PRMT1, the primary type I arginine methyltransferase, significantly increases in LSC-enriched CD34+CD38- populations relative to normal counterparts. Genetic PRMT1 depletion blocked AML CD34+ cell survival, and had more potent effects in AML cells from patients harboring FLT3-ITD. Our genome wide analysis of gene expression and PRMT1 conditional KO mouse study confirmed that PRMT1 preferentially cooperates with FLT3-ITD contributing to AML cell maintenance. Mechanistically, PRMT1 catalyzed FLT3-ITD protein methylation at arginines 972/973, and PRMT1 promoted leukemia cell growth in a FLT3 methylation-dependent manner. Moreover, effects of FLT3-ITD methylation in AML cells were in part due to crosstalk with FLT3-ITD phosphorylation at tyrosine 969 (Y969). Importantly, FLT3 methylation persisted in FLT3-ITD+ AML cells following TKI (AC220) treatment, indicating that methylation occurs independently of kinase activity. Finally, in both patient-derived xenograft (PDX) and murine AML models, combined administration of AC220 with a type I PRMT inhibitor (MS023) enhanced elimination of FLT3-ITD+ AML relative to AC220 treatment alone. Our study demonstrates that PRMT1-mediated FLT3 methylation promotes LSC activity and suggests that combining PRMT1 inhibition with FLT3 TKI treatment could be a promising approach to selectively target FLT3-ITD+ LSCs.

2021-11-10 | GSE122435 | GEO

Next generation sequencing identifies small RNA expression in FLT3-ITD+ AML (MV4-11) cell lines

Project description:The expression level of microRNAs in FLT3-ITD+ AML is unknown. Using empty vector (EV) lentiviral CRISPR-Cas9 infected FLT3-ITD+ AML cell lines (MV4-11 cells), we performed next generation RNA sequencing on small RNAs to determine microRNA expression level in these cells. We found a variety of evolutionarily conserved and non-conserved microRNAs expressed in our cells of interest. Small RNAseq on EV lentiviral CRISPR-Cas9 infected MV4-11 cell lines was performed on triplicate cultures.

2016-07-01 | E-GEOD-71543 | biostudies-arrayexpress

Expression profile of wild type (WT) vs miR-155-/- in FLT3-ITD+ AML (MV4-11) cell lines

Project description:The expression profile in miR-155-/- FLT3-ITD+ AML is unknown. Using empty vector (EV) or two distinct miR-155 (S3 or S10) lentiviral CRISPR-Cas9 infected FLT3-ITD+ AML cell lines (MV4-11 cells), we performed next generation RNA sequencing to determine the expression profile in these cells dependent on miR-155. We found a number of pathways dysregulated, including STAT5 activation. RNAseq was performed on EV or miR-155 lentiviral CRISPR-Cas9 infected MV4-11 cell lines in triplicate cultures.

2016-07-01 | E-GEOD-71541 | biostudies-arrayexpress

FLT3 inhibition upregulates HDAC8 via FOXO to inactivate p53 and promote maintenance of FLT3-ITD+ acute myeloid leukemia

Project description: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. Therefore, elucidating the mechanisms underlying FLT3-ITD+ AML maintenance and drug resistance is essential to develop novel, effective treatment strategies. Here, we demonstrate that FLT3 inhibition induces histone deacetylase 8 (HDAC8) upregulation through FOXO1 and FOXO3-mediated transactivation in FLT3-ITD+ AML cells. Upregulated HDAC8 deacetylates and inactivates p53, leading to leukemia maintenance and drug resistance upon TKIs treatment. Genetic or pharmacological inhibition of HDAC8 re-activates p53, abrogates leukemia maintenance and significantly enhances TKI-mediated elimination of FLT3-ITD+ AML cells. Importantly, in FLT3-ITD+ AML patient-derived xenograft models, the combination of FLT3 TKI (AC220) with a HDAC8 inhibitor (22d) significantly inhibits leukemia progression and effectively reduces primitive FLT3-ITD+ AML cells. Moreover, we extend these findings to an AML subtype harboring another tyrosine kinase activating mutation. In conclusion, our study demonstrates that HDAC8 upregulation as an important mechanism to resist TKIs and promote leukemia maintenance, and suggests that combining HDAC8 inhibition with TKI treatment could be a promising strategy to treat FLT3-ITD+ AML and other tyrosine kinase mutation-harboring leukemias.

2020-02-13 | GSE138057 | GEO

PRMT1-mediated FLT3 arginine methylation promotes FLT3-ITD+ Acute Myeloid Leukemia maintenance

Project description:PRMT1-mediated FLT3 arginine methylation promotes FLT3-ITD+ Acute Myeloid Leukemia maintenance

| PRJNA532633 | ENA

Next generation sequencing identifies small RNA expression in FLT3-ITD+ AML (MV4-11) cell lines

2016-07-01 | GSE71543 | GEO