Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

ABSTRACT: Immunotherapy-resistant acute lymphoblastic leukemia cells exhibit reduced CD19 and CD22 expression and BTK pathway dependency

PROVIDER: PRJNA1073528 | ENA |

REPOSITORIES: ENA

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
	SRR27873617.fastq.gz	Fastqsanger.gz
	SRR27873618.fastq.gz	Fastqsanger.gz

Items per page:

1 - 2 of 2

Similar Datasets

Immunotherapy-resistant acute lymphoblastic leukemia cells exhibit reduced CD19 and CD22 expression and BTK pathway dependency [RNA-seq]

Project description:Immunotherapy-resistant acute lymphoblastic leukemia cells exhibit reduced CD19 and CD22 expression and BTK pathway dependency [RNA-seq]

| PRJNA1074409 | ENA

Immunotherapy-resistant acute lymphoblastic leukemia cells exhibit reduced CD19 and CD22 expression and BTK pathway dependency [ATAC-seq]

Project description:Immunotherapy-resistant acute lymphoblastic leukemia cells exhibit reduced CD19 and CD22 expression and BTK pathway dependency [ATAC-seq]

| PRJNA1074410 | ENA

Immunotherapy-resistant acute lymphoblastic leukemia cells exhibit reduced CD19 and CD22 expression and BTK pathway dependency [ATAC-seq]

Project description:While therapies targeting CD19 by antibodies, CAR-T cells and T cell engagers have improved the response rates in B-cell malignancies; the emergence of resistant cell populations with low CD19 expression can lead to relapsed disease. We developed an in vitro model of adaptive resistance facilitated by chronic exposure of leukemia cells to a CD19-immunotoxin. Single-cell (sc) RNAseq showed increase in transcriptionally distinct CD19low populations in resistant cells. Mass cytometry demonstrated that CD22 was also decreased in these CD19low resistant cells. ATAC-seq showed decreased chromatin accessibility at promoters of both CD19 and CD22 in the resistant cell populations. Combined loss of both CD19 and CD22 antigens was validated in samples from pediatric and young adult patients with B-ALL that relapsed after CD19 CAR-T targeted therapy. Functionally, resistant cells were characterized by slower growth and lower basal levels of MEK activation. CD19low resistant cells exhibited preserved B cell receptor signaling and were more sensitive to both BTK and MEK inhibition. These data demonstrate that resistance to CD19 immunotherapies can result in decreased expression of both CD19 and CD22 and can result in dependency on BTK pathways.

2024-03-06 | GSE255305 | GEO

Immunotherapy-resistant acute lymphoblastic leukemia cells exhibit reduced CD19 and CD22 expression and BTK pathway dependency [RNA-seq]

2024-03-06 | GSE255306 | GEO

An Informatic Approach to Chimeric Antigen Receptor Discovery Integrates Proteomics and Transcriptomics to Identify Novel Combinatorial Pairs

Project description:Chimeric antigen receptor (CAR) therapy targeting CD19 yielded remarkable outcomes in patients with acute lymphoblastic leukemia. To identify potential CAR targets in acute myeloid leukemia (AML), we probed the AML surfaceome for over-expressed molecules with potentially tolerable systemic expression. We integrated large transcriptomics and proteomics data sets from malignant and normal tissues, and developed an algorithm to identify potential targets expressed in leukemia stem cells, but not in normal CD34+CD38– hematopoietic cells, T cells or vital tissues. As these investigations did not uncover candidate targets with a profile as favorable as CD19, we developed a generalizable combinatorial targeting strategy fulfilling stringent efficacy and safety criteria. Our findings indicate that several target pairings hold great promise for CAR therapy of AML.

2017-10-24 | PXD007552 | Pride

Expression data of human CD19pos B lymphocytes (B) and CD19negCD22neg non-B cells (ENV) from non tumoral reactive lymph nodes (RLN), tonsils (TONS) or follicular lymphoma (FL)

Project description:GEP on Affymetrix U133+2.0 microarrays was performed on ex vivo CD19+ B lymphocytes or CD19-CD22- fractions from reactive or FL lymph nodes or normal tonsils.

2019-05-27 | GSE107367 | GEO

PU.1 and Spi-B oppose transformation of pre-B cells through activation of key genes involved in B cell receptor signaling

Project description:Deletion of genes encoding the E26 transformation-specific (ETS) transcription factors, PU.1 and Spi-B, in B cells (CD19-CreDPB mice) leads to acute lymphoblastic leukemia at 100% incidence and with a median survival of 21 weeks. To identify pathways of leukemic transformation, we compared gene expression in leukemia cells from CD19-CreDPB mice (CD19-CreDPB B220- B-ALL) with B cells from Spi-B knockout (Control DB) or B cells from CD19-CreDPB mice (CD19-CreDPB B220+ B cell)

2014-11-12 | GSE48891 | GEO

Regulatory programs of B-cell activation and germinal center reaction allow for B-ALL escape from CD19 CAR T-cell therapy

Project description:CAR T-cell therapy has led to tremendous successes in the treatment of B-cell malignancies. However, 30%-50% of treated patients relapse – often with reduced target antigen expression. We report that anti-CD19 CAR T-cells cause a rapid reduction of CD19 expression within hours in CAR-T exposed CD19+ B-ALL cells. Initially, anti-CD19 CAR T-cells cause CD19 clusters at the T-cell – leukemia cell interface followed by CD19 internalization and decreased CD19 surface expression. Subsequently, CD19 expression is repressed by transcriptional rewiring. Using single-cell RNA-seq and single-cell ATAC-seq we demonstrate that a subset of CD19low cells that are refractory to CAR T-cell killing employ transcriptional programs of physiological B-cell activation and germinal center reaction in order to sustain decreased CD19 expression. Inhibiting B-cell activation programs with the BTK inhibitor ibrutinib increased the cytotoxic efficacy of anti-CD19 CAR T-cells without effecting CAR T-cell viability. These results demonstrate transcriptional plasticity as an underlying mechanism of CAR T-resistance and highlight the importance of combining CAR T-cell therapy with targeted therapies that aim to overcome this plasticity.

2022-06-09 | GSE176418 | GEO

Mutations and RNA-binding proteins controlling CD19 splicing and CART-19 therapy resistance: Minigene library DNA-seq

Project description:We developed a massively parallel reporter assay to determine the splicing effects of all mutations in the region comprising CD19 exons 1-3. Despite the great success of CART-19 (chimeric antigen receptor-armed autologous T-cells) immunotherapy to treat B-cell acute lymphoblastic leukaemia (B-ALL), many patients relapse due to loss of the targeted CD19 epitope. Since epitope loss can be caused by CD19 exon 2 mis-splicing, we set out to learn the regulatory code that controls CD19 alternative splicing.

2022-06-05 | GSE182891 | GEO

Mutations and RNA-binding proteins controlling CD19 splicing and CART-19 therapy resistance: PTBP1 iCLIP2 in NALM-6 cells

2022-06-05 | GSE182893 | GEO