Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Enhancer-activated RET confers protection against oxidative stress to KMT2A-rearranged acute myeloid leukemia.

ABSTRACT: Enhancer-activated RET confers protection against oxidative stress to KMT2A-rearranged acute myeloid leukemia.

PROVIDER: PRJNA1010364 | ENA |

REPOSITORIES: ENA

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
	SRR25782135_1.fastq.gz	Fastqsanger.gz
	SRR25782135_2.fastq.gz	Fastqsanger.gz
	SRR25782136_1.fastq.gz	Fastqsanger.gz
	SRR25782136_2.fastq.gz	Fastqsanger.gz
	SRR25782137_1.fastq.gz	Fastqsanger.gz

Items per page:

1 - 5 of 12

Similar Datasets

Enhancer-activated RET confers protection against oxidative stress to KMT2A-rearranged acute myeloid leukemia.

Project description:KMT2A-MLLT3, a fusion protein formed by the t(9;11) translocation in acute myeloid leukemia, is an epigenetic transcription factor that is known to regulate a unique leukemic gene expression profile. We show that rearranged during transfection (RET) proto-oncogene is highly overexpressed in the KMT2A-MLLT3 subgroup. In addition to biochemical studies, the RNA-seq and ATAC seq analyses have been performed in KMT2A-MLLT3 positive MOLM-13 AML cell line, compared to the umbilical cord blood-driven CD34+ hematopoietic stem progenitor cells.

2024-03-04 | GSE241867 | GEO

Enhancer-activated RET confers protection against oxidative stress to the MLL-rearranged acute myeloid leukemia cells

Project description:RET expression is upregulated in AML subtypes harboring genetic fusions of MLL-1 genes compared to age-matched healthy donors and other AML subtypes. In addition, we identify a novel epigenetic mechanism of RET overexpression in MLL-rearranged AML.

2024-03-04 | GSE241738 | GEO

Enhancer-activated RET confers protection against oxidative stress to the MLL-rearranged acute myeloid leukemia cells

Project description:Enhancer-activated RET confers protection against oxidative stress to the MLL-rearranged acute myeloid leukemia cells

| PRJNA1009434 | ENA

Phosphoproteomics of primary acute myeloid leukemia cells with rearranged KMT2A

Project description:Acute myeloid leukemia (AML) is a disease with poor outcome but patients harbouring certain chromosomal rearrangements or complex karyotypes have particularly adverse prognosis. For these patients, targeted therapies have not yet made a significant clinical impact. To understand the molecular landscape of poor risk AML we profiled 55 poor risk AML patients using a multiomics approach that included transcriptomics (n=39), proteomics (n=55), phosphoproteomics (n=55) and an ex vivo drug sensitivity screening (482 compounds tested in at least 30 patients). We identified a phosphoproteomics signature that define two biologically distinct groups of KMT2A rearranged leukaemia, which we term MLLGA and MLLGB. MLLGA presented increased DOT1L phosphorylation, HOXA gene expression, CDK1 activity and phosphorylation of proteins involved in RNA metabolism, replication and DNA damage when compared to MLLGB and no KMT2A rearranged samples. MLLGA was particularly sensitive to 15 compounds including genotoxic drugs and inhibitors of mitotic kinases and IMPDH relative to other cases. The expression of IMPDH2 and multiple nucleolar proteins was higher in MLLGA and correlated with the response to IMPDH inhibition in KMT2A rearranged leukaemia, suggesting a role of the nucleolar activity in sensitivity to IMPDH inhibition. In summary, our multilayer molecular profiling of poor risk AML matched to the response to hundreds of compounds identified a phosphoproteomics signature that define two biologically and phenotypically distinct groups of KMT2A rearranged leukaemia. These data provide a rationale for the development of specific therapies for KMT2A subgroups characterised by the MLLGA phosphoproteomics signature identified in this study.

2023-03-11 | PXD036669 | Pride

Anti-tumor activity and acquired resistance mechanism of Dovitinib (TKI258) in RET rearranged lung adenocarcinoma

Project description:RET rearrangement is a newly identified oncogenic mutation in lung adenocarcinoma (LADC). Activity of dovitinib (TKI258), a potent inhibitor of FGFR, VEGFR, and PDGFR, in RET-rearranged LADC has not been reported. The aims of the study are to explore anti-tumor effects and mechanisms of acquired resistance of dovitinib in RET-rearranged LADC. Using structural modeling and in vitro analysis, we demonstrated that dovitinib induced cell cycle arrest at G0/G1 phase and apoptosis by selective inhibition of RET kinase activity and ERK1/2 signaling in RET-rearranged LC-2/ad cells. Strong anti-tumor effect of dovitinib was observed in LC-2/ad tumor xenograft model. To identify the acquired resistance mechanisms to dovitinib, LC-2/ad cells were exposed to increasing concentrations of dovitinib to generate LC-2/ad DR cells. Gene set enrichment analysis of gene expression and receptor tyrosine kinase assay revealed that Src, a central gene in focal adhesion , was activated in LC-2/ad DR cells. Saracatinib, a src kinase inhibitor, suppressed ERK1/2 phosphorylation and growth of LC-2/ad DR cells. Taken together, these findings suggest that dovitinib can be a potential therapeutic option for RET-rearranged LADC, in which acquired resistance to dovitinib can be overcome by targeting Src. To identify potential mechanisms of acquired resistance to dovitinib, we established LC-2/ad DR cells with acquired resistance to dovitinib by exposing LC-2/ad cells to increasing doses of dovitinib. LC-2/ad DR cells showed strong resistance to dovitinib (IC50> 3 μmol/L). Next, LC-2/ad and LC-2/ad DR cells were subjected to genome-wide gene expression profiling using cDNA microarray.

2015-09-01 | E-GEOD-69226 | biostudies-arrayexpress

RNA-seq analysis of human KMT2A rearranged MV4;11 AML cell line treated with DOT1L and/or EZH2 inhibitor

Project description:The histone methyltransferases DOT1L (H3K79me1,2,3 KMT, "activating" chromatin mark) and EZH2 (H3K27me1,2,3 KMT, "silencing" mark) have both been shown to be required for growth and survival of KMT2A rearranged AML cells. Both KMTs have been shown to modulate expression of HOXA cluster genes, albeit for EZH2 this has not been shown in the context of KMT2A rearranged AML, but in other subtypes of AML. We asked what transcriptional effects dual inhibition of DOT1L and EZH2 has in KMT2A rearranged AML.

2019-07-17 | GSE134369 | GEO

RNA-seq analysis of human KMT2A rearranged Molm14 AML cell line treated with DOT1L and/or EZH2 inhibitor

2020-04-29 | GSE149520 | GEO

KMT2A-rearranged leukemia proteomics

Project description:Activating mutations in kinase/PI3K/RAS signaling pathways are common in acute leukemia with KMT2A rearrangements (KMT2A-R). These mutations are often subclonal and their biological impact remain unclear. Using a retroviral acute myeloid leukemia model, we demonstrate that NRASG12D, FLT3ITD, and FLT3N676K accelerates KMT2A-MLLT3 leukemia onset. Importantly, also the presence of subclonal FLT3N676K in KMT2A-R leukemic cells shorten disease latency, possibly by providing stimulatory factors such as Mif. Acquired de novo mutations in Braf, Cbl, Kras, and Ptpn11 were identified in KMT2A-MLLT3 driven leukemia and favored clonal expansion. KMT2A-MLLT3 leukemia with an activating mutation enforce Myc- and Myb transcriptional modules, whereas KMT2A-MLLT3 leukemias lacking activating mutations displayed upregulation of signal transduction pathways. Our results provide new insight into the biology of KMT2A-R leukemia and highlights the importance of activated signaling as a contributing driver in this disease.

2018-05-02 | PXD008213 | Pride

Effect of methionine restriction on gene expression of non-KMT2A-rearranged NALM-6 and KMT2A-rearranged SEM BCP-ALL cell lines

Project description:Current intensive chemotherapy regimens have improved overall survival in pediatric acute lymphoblastic leukemia but fail to cure some high-risk patient subgroups. While exploring amino acid depletion strategies, we observed that KMT2A-rearranged (KMT2A-r) leukemia, an aggressive subset with a dismal prognosis, is particularly vulnerable to perturbations of the methionine cycle. We demonstrated that this methionine dependency is primarily driven by an increased need for S-adenosylmethionine to maintain the hypermethylated state of KMT2A-r leukemias. Important pro-survival KMT2A-r target genes are repressed under methionine restriction, which, combined with other downstream metabolic changes, results in rapid cell death. FIDAS-5, an orally active methionine adenosyltransferase 2A (MAT2A) inhibitor, successfully impaired leukemia progression in patient-derived xenograft models, and a high-throughput drug screen revealed a strong synergy between MAT2A inhibition and histone deacetylase inhibitors. Our results identified the methionine cycle as a targetable vulnerability in KMT2A-r leukemia, which may increase the efficacy of epigenetic targeting agents.

2024-12-31 | GSE234806 | GEO

Anti-tumor activity and acquired resistance mechanism of Dovitinib (TKI258) in RET rearranged lung adenocarcinoma

2015-09-01 | GSE69226 | GEO