Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

FBXO11 is a candidate tumor suppressor in the leukemic transformation of myelodysplastic syndrome

ABSTRACT: FBXO11 is a candidate tumor suppressor in the leukemic transformation of myelodysplastic syndrome

PROVIDER: PRJNA658804 | ENA |

REPOSITORIES: ENA

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
	SRR12504966_1.fastq.gz	Fastqsanger.gz
	SRR12504966_2.fastq.gz	Fastqsanger.gz
	SRR12504967_1.fastq.gz	Fastqsanger.gz
	SRR12504967_2.fastq.gz	Fastqsanger.gz
	SRR12504968_1.fastq.gz	Fastqsanger.gz

Items per page:

1 - 5 of 24

Similar Datasets

FBXO11 is a candidate tumor suppressor in the leukemic transformation of myelodysplastic syndrome

Project description:This experiment is assocaited with a publication defining a tumor supressor role of FBXO11 in the transformation of MDS. We observe decreased expression of FBXO11 is associated with transformation to secondary AML.

2020-08-24 | GSE156708 | GEO

FBXO11 is a candidate tumor suppressor in the leukemic transformation of myelodysplastic syndrome.

Project description:Myelodysplastic syndrome (MDS) is a heterogeneous myeloid malignancy characterized by blood cell morphological dysplasia, ineffective clonal hematopoiesis, and risk of transformation to secondary acute myeloid leukemia (sAML). A number of genetic abnormalities have been identified in MDS and sAML, but sensitive sequencing methods can detect these mutations in nearly all healthy individuals by 60 years of age. To discover novel cellular pathways that accelerate MDS and sAML, we performed a CRISPR/Cas9 screen in the human MDS-L cell line. We report here that loss of the F-Box protein FBXO11, a component of the SCF ubiquitin ligase complex, confers cytokine independent growth to MDS-L cells, suggesting a tumor suppressor role for FBXO11 in myeloid malignancies. Putative FBXO11 substrates are enriched for proteins with functions in RNA metabolism and, of note, spliceosome mutations that are commonly found in MDS/sAML are rare in patients with low FBXO11 expression. We also reveal that loss of FBXO11 leads to significant changes in transcriptional pathways influencing leukocyte proliferation, differentiation, and apoptosis. Last, we find that FBXO11 expression is reduced in patients with secondary AML. We conclude that loss of FBXO11 is a mechanism for disease transformation of MDS into AML, and may represent a future therapeutic target.

| S-EPMC7538974 | biostudies-literature

Pseudouridine-modified tRNA fragments repress malignant protein synthesis and predict leukemic progression in myelodysplastic syndrome

Project description:Transfer RNA (tRNA)-derived fragments (tRF) are emerging small noncoding (nc) RNAs that, while commonly altered in cancer, have poorly defined roles in tumorigenesis. Here we show that pseudouridylation (Ψ) of a stem-cell-enriched tRF subtype, mTOG, selectively inhibits malignant protein synthesis programs, thereby promoting engraftment and differentiation of myelodysplastic syndrome (MDS) hematopoietic stem and progenitor cells (HSPC). Building on evidence that mTOG-Ψ target the polyadenylate-binding protein cytoplasmic 1 (PABPC1), we employed HDX-MS to reveal critical interactions between mTOG and functional RNA-recognition motif (RRM) domains in PABPC1. Mechanistically, this hinders the recruitment of the translational co-activator PABPC1-interacting protein 1 (PAIP1) and strongly represses translation of transcripts sharing 5’UTR pyrimidine-enriched sequences (PES), including 5’ terminal oligopyrimidine tracts (TOP) that encode protein machinery components, and are frequently altered in cancer. Significantly, mTOG dysregulation leads to aberrantly increased 5’PES mRNA translation in malignant MDS-HSPC and is clinically associated with leukemic transformation and reduced patient survival. Taken together, these results define a critical role for tRF and Ψ in difficult-to-treat subsets of MDS characterized by high risk of progression to acute myeloid leukemia.

2021-12-20 | PXD023122 | Pride

HOXA9 Reprograms the Enhancer Landscape During Leukemic Transformation

Project description:HOXA9 Reprograms the Enhancer Landscape During Leukemic Transformation

| PRJNA401435 | ENA

LKB1/STK11 is a tumor suppressor in the leukemic transformation of myeloproliferative neoplasms

Project description:LKB1/STK11 is a tumor suppressor in the leukemic transformation of myeloproliferative neoplasms

| PRJNA727871 | ENA

CBFA2T3-GLIS2 oncogenic fusion is sufficient for leukemic transformation

Project description:CBFA2T3-GLIS2 oncogenic fusion is sufficient for leukemic transformation

| PRJNA753108 | ENA

4T1 cells with Control vs SNAIL vs SNAIL/FBXO11

Project description:Transcriptional profiling of mouse 4T1 breast cancer cells stably tranduced with pLEX-MCS based lentivirus. Three groups were compared, Vector cells, SNAIL expressing cells; and SNAIL+FBXO11 expressing cells. SNAIL expression induced strong EMT phenotype while SNAIL/FBXO11 reversed cells back to epithelial cells.

2014-12-01 | GSE50887 | GEO

Expression of mutant Asxl1 perturbs hematopoiesis and promotes susceptibility to leukemic transformation

Project description:Additional Sex Combs Like 1 (ASXL1) is frequently mutated in myeloid malignancies and clonal hematopoiesis of indeterminate potential (CHIP). Although loss of ASXL1 promotes hematopoietic transformation, there is growing evidence that ASXL1 mutations might confer an alteration of function. Here we identify that physiological expression of a C-terminal truncated Asxl1 mutant in vivo using conditional knock-in (KI) results in myeloid skewing, age-dependent anemia, thrombocytosis, and morphologic dysplasia. Although expression of mutant Asxl1 altered the functions of hematopoietic stem cells (HSCs), it maintained their survival in competitive transplantation assays and increased susceptibility to leukemic transformation by co-occurring RUNX1 mutation or viral insertional mutagenesis. KI mice displayed substantial reductions in H3K4me3 and H2AK119Ub without significant reductions in H3K27me3, distinct from the effects of Asxl1 loss. ChIP-seq analysis demonstrated opposing effects of wildtype and mutant Asxl1 on H3K4me3. These findings reveal that ASXL1 mutations confer HSCs with an altered epigenome and increase susceptibility for leukemic transformation, presenting a novel model for CHIP.

2018-02-28 | GSE111067 | GEO

The signaling axis atypical protein kinase C l/i-Satb2 mediates leukemic transformation of B-cell progenitors

Project description:Oncogene driven transformation of leukemic progenitors results in B-acute lymphoblastic leukemia. Genetic deletions at specific hotspots are driven by recombination of epigenetically repressed loci and cause B cell transformation, and epigenetically regulated transcriptional plasticity has been proposed as a mechanism of differentiation arrest and resistance to therapy. The upstream signals driving epigenetic silencing have not been elucidated. BCR-ABL leukemias are initiated by leukemic stem cells/progenitors, and their modeling in vivo represents an opportunity for the identification of the epigenetic progress contributing to lineage leukemogenesis. We have found that primary human and murine BCR-ABL+ leukemic progenitors have increased activation of Cdc42 and the downstream atypical protein kinase C (aPKC). While the isoform aPKCz behaves as a leukemic suppressor, aPKCl/i is critically required for oncogenic progenitor proliferation, survival, and B cell differentiation arrest, but not for normal B cell lineage differentiation. We found that in vitro and in vivo B cell transformation by BCR-ABL requires the downregulation of key genes in the B-cell differentiation program through an aPKCl/i-dependent Etv5/Satb2 chromatin repressive signaling complex. Thus genetic or pharmacological targeting of aPKC impairs human oncogenic addicted leukemias in vitro and in vivo. Therefore, the aPKCl/i-SATB2 signaling cascade is required for leukemic BCR-ABL+ B-cell progenitor transformation and is amenable to non-BCR-ABL kinase inhibition.

2018-10-10 | GSE121018 | GEO

HMLEN cells with Vector Control vs SNAIL vs SNAIL/FBXO11

Project description:Transcriptional profiling of mouse HMLEN breast cancer cells (HMLE cells transformed with -Neu oncogene) stably tranduced with pLEX-MCS based lentivirus. Three groups were compared, Vector cells, SNAIL expressing cells; and SNAIL+FBXO11 expressing cells. SNAIL expression induced strong EMT phenotype while SNAIL/FBXO11 reversed cells back to epithelial cells.

2014-12-01 | GSE50888 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data