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Epigenetic drugs selectively target a population of AML cells which are positive for CD123 cell surface markers and are chemoresistant

ABSTRACT: Epigenetic drugs selectively target a population of AML cells which are positive for CD123 cell surface markers and are chemoresistant

PROVIDER: PRJNA472052 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR6380211.fastq.gz	Fastqsanger.gz
	SRR6380212.fastq.gz	Fastqsanger.gz
	SRR6380213.fastq.gz	Fastqsanger.gz
	SRR7182924_1.fastq.gz	Fastqsanger.gz
	SRR7182924_2.fastq.gz	Fastqsanger.gz

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Similar Datasets

Epigenetic drugs selectively target a population of AML cells which are positive for CD123 cell surface markers and are chemoresistant I

Project description:Epigenetic drugs selectively target a population of AML cells which are positive for CD123 cell surface markers and are chemoresistant I

| PRJNA422583 | ENA

Epigenetic drugs selectively target a population of AML cells which are positive for CD123 cell surface markers and are chemoresistant II

Project description:Epigenetic drugs selectively target a population of AML cells which are positive for CD123 cell surface markers and are chemoresistant II

| PRJNA472053 | ENA

Epigenetic drugs selectively target a population of AML cells which are positive for CD123 cell surface markers and are chemoresistant

Project description:This SuperSeries is composed of the SubSeries listed below.

2020-08-28 | GSE114649 | GEO

Epigenetic drugs selectively target a population of AML cells which are positive for CD123 cell surface markers and are chemoresistant II

Project description:Gene expression profiling was performed on OCI-AML2 R50 drug resistant leukemia cell line before or after Romidepsin treatment.

2020-08-28 | GSE114648 | GEO

Epigenetic drugs selectively target a population of AML cells which are positive for CD123 cell surface markers and are chemoresistant I

Project description:Global gene expression profiling was performed on OCI-AML2 leukemia cell line, R3 and R50 drug resistant cell lines.

2020-08-28 | GSE108142 | GEO

RNA-seq data analysis of CD123 loss samples

Project description:Molecular analysis of CD123 loss following UCART123 treatment.

2022-03-14 | GSE198471 | GEO

Evaluation of the impact of scFv on functionality and safety of 3rd generation CD123 CAR T cells

Project description:Chimeric Antigen Receptor T cells express an extracellular domain consisting of a single-chain fragment variable (scFv) targeting a surface tumor-associated antigen (TAA), it is important to select scFv regarding safety profile through evaluation of the efficacy/toxicity balance, especially in cases where the target antigen is also expressed on healthy cells. Here, we developed five CAR T cells targeting CD123 (CD123 CAR-T) by substituting only the scFv, looking for differences in terms of efficacy and on-target/off-tumor effects. Using in vitro models, we found that three of the five CD123 CAR-T were more cytotoxic against leukemic cells, without increasing lysis of monocytes or endothelial cells. Using the Incucyte system, we confirmed the low cytotoxicity of CD123 CAR-T on endothelial cells. Hematotoxicity evaluated by progenitor culture and CD34 cell lysis showed that two of the five CD123 CAR-T were less cytotoxic against HSC, and we confirmed in a humanized mouse model that CD123- cells were not eliminated by the CD123 CAR-T. These two CD123 CAR-T reduced tumor infiltration and increased overall survival of mice in three in vivo models of BPDCN. Moreover, in BPDCN aggressive model, bulk RNA-sequencing analysis showed that these CD123 CAR-T upregulated genes associated with cytotoxicity and activation/exhaustion a few days after the injection. Finally, we were able to produce CD123 CAR-T selected previously from patient T cells. Together, these results emphasize the importance of screening different scFv for the development of CAR-T constructs, to select the one with the optimal risk-benefit ratio for clinical development.

2024-06-03 | GSE253738 | GEO

Effect of CD33 and/or CD123 KO in the NPM1-mutated AML cell line OCI-AML3

Project description:To reveal which pathways linked to CD33 and CD123 overexpression could be involved in leukemic proliferation, we performed unbiased bulk RNA sequencing comparison between OCI-AML3 wt and CD123 and or CD33 KO clones

2022-07-25 | GSE209518 | GEO

Proteomic characterization of CD34+ CD123+ stem cells from patients with acute myeloid leukemia

Project description:The comparative characterization of hematopoietic stem cells from healthy stem cell donors and patients with acute myeloid leukemia on a proteome level has the potential to reveal differentially regulated proteins which might be candidates for specific immunotherapy target molecules. Exemplarily, we analyzed the proteome of the cytosolic and the membrane fraction of CD34 and CD123 co-expressing FACS-sorted leukemic progenitors from five patients with acute myeloid leukemia employing mass spectrometry. As a reference, CD34+CD123+ normal hematopoietic progenitor cells from five healthy stem cell donors were analyzed. In this TMT 10-plex labeling based approach 2068 proteins were identified with 256 proteins differentially regulated in one or both cellular compartments. This study demonstrates the feasibility of a mass spectrometry based proteomic approach to detect differentially expressed proteins in two compartment fractions of leukemic stem cells as compared to their healthy stem cell counterparts.

2018-02-19 | PXD008378 | Pride

Vaccine Educated T cells and a CD123 Bi-Specific T-Cell Engager for Treatment of Acute Myeloid Leukemia

Project description:Immunotherapy strategies in acute myeloid leukemia remain limited. CD123 is a promising target as it is overexpressed in myeloid blasts. This preclinical work investigates possible synergy of CD123 T cell engager and dendritic cell based vaccine, which can induce the expansion of leukemia specific T cells. Efficacy of combination therapy was evaluated in a patient-derived xenograft model and the infused T cells were later collected for single cell rnaseq to determine effects on gene expression pathways and clonality. In the present study, we demonstrated that the combination of DC/AML fusion vaccine and a CD123 T cell engager SAR440234 led to an increase in tumor specific T cell immunity and enhanced anti-leukemia effect in vitro. Furthermore, the combination treatment was shown to increase cytotoxic T cell subsets and clonotypic expansion and eradicate disease in vivo. Thus the combination of T cell engager and vaccination or adoptive T cell transfer is a novel approach that merits further investigation in clinical trials.

2025-06-06 | GSE265780 | GEO

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