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Expression and incorporation of microRNA in exosomes released by leukemia cells under room air and hypoxia

ABSTRACT: We recently showed that exosomes from primary AML cells and cell lines have potent regulatory capacity and we hypothesized that leukemia cell exosome trafficking might account for the suppression of residual hematopoietic stem and progenitor cells (HSPC) in the leukemic niche. Here we studied Molm-14 cells in in vitro experiments using purified exosomes under carefully calibrated low-oxygen conditions. This approach revealed the active regulation of stromal- and hematopoietic progenitor cell function. Systematic analysis of AML exosomes identified a panel of differentially enriched hypoxia-responsive miRNAs, including miR-210, -155, and -146a.

ORGANISM(S): synthetic construct Homo sapiens

PROVIDER: GSE55025 | GEO | 2014/02/20

SECONDARY ACCESSION(S): PRJNA238620

REPOSITORIES: GEO

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Expression and incorporation of microRNA in exosomes released by leukemia cells under room air and hypoxia

Project description:We recently showed that exosomes from primary AML cells and cell lines have potent regulatory capacity and we hypothesized that leukemia cell exosome trafficking might account for the suppression of residual hematopoietic stem and progenitor cells (HSPC) in the leukemic niche. Here we studied Molm-14 cells in in vitro experiments using purified exosomes under carefully calibrated low-oxygen conditions. This approach revealed the active regulation of stromal- and hematopoietic progenitor cell function. Systematic analysis of AML exosomes identified a panel of differentially enriched hypoxia-responsive miRNAs, including miR-210, -155, and -146a. We cultured cells under normoxic and hypoxic conditions. Exosomes were released from the parental cells and captured. Total RNA was isolated from both exosomes and cells. Please note that the sample numbers (in the titles) do differ from pair identification (i.e. pair ID) as the pair is only in reference to the paired-t test and parental vs. released pairs.

2014-02-20 | E-GEOD-55025 | biostudies-arrayexpress

Extracellular vesicles impose quiescence and confer DNA-damage on residual HSC in the AML niche

Project description:To understand the mechanism by which AML-EVs may enforce quiescence, we performed tandem mass tag (TMT) proteomic profiling of in vitro cultured c-Kit+ hematopoietic stem and progenitor cells (HSPC) (to obtain the minimum required amount of protein lysates) treated with extracellular vesicles (EVs) for 48 hours from human HL-60 or Molm-14 cell cultures versus controls.

2019-06-24 | PXD013688 | Pride

Expression and exosome incorporation of microRNA by leukemia versus nonmalignant hematopoietic progenitors

Project description:Exosomes are paracrine regulators of the tumor microenvironment. However, their complex cargo can hamper an understanding of their specific action in target cells. We therefore sought to identify the changes in exosome miRNA content that occur with malignant transformation by comparing two myeloid cancer cell lines to their nonmalignant predecessors, CD34+ human hematopoietic progenitor cells. We employed microarrays to evaluate which miRNA are present at altered concentrations before and after transformation as well as before and after incorporation into exosomes.

2016-08-18 | GSE85769 | GEO

The protein interactomes of Acute Myeloid Leukemia-associated oncogenic fusion proteins predict potential mechanisms of action

Project description:TurboID (biotin proximity ligase) was fused to AML-associated oncofusions (PML::RARA, RUNX1::RUNX1T1, CBFB::MYH11), wildtype NPM1, or mutated NPMc and expressed in murine hematopoietic stem/progenitor cells using MSCV-based retroviruses to identify key interacting proteins in primary hematopoietic cells.

2023-08-07 | MSV000092615 | MassIVE

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

Expression data from human A549 cells and exosomes under room air (RA) or intermittent hypoxia (IH)

Project description:Studies have shown that IH may promote the development of non-small-cell lung cancer (NSCLC), Exosomes carry specific proteins, lipids, small molecule RNAs (miRNAs) as well as other bioactive substances, which play an important role in tumor growth. The role of exosomal miRNAs in the promotion of tumor development by IH has not been studied.

2021-07-29 | GSE181067 | GEO

FBXO9 in Murine Inversion 16 AML

Project description:The hematopoietic system is maintained throughout life by hematopoietic stem cells that are capable of differentiation to all hematopoietic lineages. An intimate balance between self-renewal, differentiation, and quiescence is required to maintain hematopoiesis. Disruption of this balance can result in hematopoietic malignancy, including acute myeloid leukemia (AML). FBXO9, from the F-box ubiquitin E3 ligases, is down-regulated in patients with AML compared to normal bone marrow. FBXO9 is a substrate recognition component of the Skp1-Cullin-F-box (SCF)-type E3 ligase complex. FBXO9 is highly expressed in hematopoietic stem and progenitor populations, which contain the tumor-initiating population in AML. In AML patients, decrease in FBXO9 expression is most pronounced in patients with the inversion of chromosome 16 (Inv(16)), a rearrangement that generates the transcription factor fusion gene, CBFB-MYH11. To study FBXO9 in malignant hematopoiesis, we generated a conditional knockout mouse model using a novel CRISPR/Cas9 strategy. Our data shows that deletion of Fbxo9 in mice expressing Cbfb-MYH11 leads to markedly accelerated and aggressive leukemia development. In addition, we find loss of FBXO9 leads to increased proteasome expression and tumors are more sensitive to bortezomib suggesting that FBXO9 expression may predict patient response to bortezomib treatment.

2019-11-27 | PXD014387 | Pride

Epigenome analysis of parental and ABT-199 resistant AML cell lines

Project description:Genome wide DNA methylation profiling of parental, ABT-199 resistant population, and ABT-199 resistant clones from 3 acute myelogenous leukemia (AML) cell lines (MOLM-13, MV-4-11, OCI-AMLO2). The Illumina Infinium MethylationEPIC Human DNA methylation Beadchip was used to obtain DNA methylation profiles across approximately 850,000 CpGs from AML cell line samples. Samples include 4 ABT-199 sensitive parental MOLM-13 population samples, 4 ABT-199 resistant MOLM-13 population samples, 3 ABT-199 resistant MOLM-13 S2 clone samples, 3 ABT-199 resistant MOLM-13 S5 clone samples, 4 ABT-199 resistant MOLM-13 S6 clone samples, 3 ABT-199 sensitive parental MV-4-11 population samples, 3 ABT-199 resistant MV-4-11 population samples, 3 ABT-199 sensitive parental OCI-AML2 population samples, 3 ABT-199 resistant OCI-AML2 population samples, 3 ABT-199 resistant OCI-AML2 S1 clone samples, 3 ABT-199 resistant OCI-AML2 S2 clone samples, 3 ABT-199 resistant OCI-AML2 S8 clone samples.

2022-01-12 | GSE193254 | GEO

Exposure with leukemia cell-derived exosomes to mouse HSPCs

Project description:Exosomes are extracellular vesicles that play crucial roles in intercullular communication. There is accumulating evidence that cancer cell-derived exosomes transfer malignant phenotypic trait to normal cells. Thus, we examined about the function of leukemia cell-derived exosomes on the normal hematopoietic stem/progenitor cells in this study.

2021-03-29 | GSE138211 | GEO

miRNA profile of exosomes released from PC-3 cells compared to parent cells

Project description:Exosomes are small extracellular vesicles released through fusion of multivesicular bodies with the plasma membrane. The aim of this study was to investigate whether there are any differences in miRNAs in exosomes secreted from the prostate cancer cell line PC-3 and in parent cells, as well as to investigate whether there are any differences in miRNAs in cell lysates from PC-3 cells and the non-cancerous prostate cell line RWPE-1. Exosomes isolated from media of PC-3 cells, RNA isolated from exosomes and parent cells, as well as from RWPE-1 cells. Using 3 biological replicates, 1 replicate per array

2015-02-12 | E-GEOD-35813 | biostudies-arrayexpress

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