Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Engineered Tr1 cells designed for clinical use can eliminate primary pediatric AML blasts

ABSTRACT: Purpose: To investigate the transcriptome of primary pediatric acute myeloid leukemia to identify molecular signatures correlated with sensitivity to LV-10 mediated killing Method: RNA sequencing of polyA enriched pediatric acute myeloid leukemia bone marrow aspirates Results: pAML killing sensitivity is associated with the expression of a myeloid maturation signature, while resistant pAMLs expressed a more stem cell-like signature Conclusions: Pediatric acute myeloid leukemia samples have different sensitivities to killing by LV-10 in vitro and the transcriptomes of killing-sensitive and killing-resistant lines differ

ORGANISM(S): Homo sapiens

PROVIDER: GSE140960 | GEO | 2020/11/10

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Paediatric Bone marrow Mesenchymal Stem cells support acute myeloid leukaemia cell survival and enhance chemoresistance via contact-independent mechanism

Project description:Pediatric mesenchymal stem cells (pMSCs) within the bone marrow (BM) niche play a crucial role in regulating pediatric acute myeloid leukemia (pAML) survival and therapy resistance. In this study, we isolated pMSCs from pAML bone marrow samples and characterized their phenotype and differentiation potential. We performed coculture experiments with pAML cells in both autologous and allogenic settings, with and without direct contact. RNA-sequencing and multiplex immunoassays revealed that pMSCs promote pAML survival through changes in gene expression, cytokine secretion, and extracellular matrix (ECM) components, specifically enhancing chemoprotection from cytarabine and Gemtuzumab Ozogamicin (GO). Inhibition of the JAK/STAT and ERK pathways using ruxolitinib (RUX) abrogated the pMSC-induced chemoprotection, suggesting a contact-independent mechanism. These findings provide new insights into how the BM microenvironment contributes to therapy resistance in pediatric AML and highlights the potential for targeting pMSC-induced signaling pathways in treatment strategies.

2024-11-11 | GSE277382 | GEO

A longitudinal single-cell atlas of treatment response in pediatric AML (scATAC-Seq)

Project description:Pediatric acute myeloid leukemia (pAML) is a disease characterized by heterogeneous cellular composition, driver alterations and prognosis. Characterization of this heterogeneity and how it affects treatment response remains relatively understudied in pediatric patients. We therefore used single-cell RNA sequencing and single-cell ATAC sequencing to profile 684,031 diagnosis, remission and relapse cells from 28 patients representing different pAML subtypes. Analysis revealed that at diagnosis, cellular compositions differed between distinct subgroups. Upon relapse, cellular hierarchies transitioned towards a more primitive state regardless of subtype. These primitive cells were distinct compared to cells at diagnosis, having underrepresentation of transcriptional programs involved in myeloid differentiation while programs commonly found in other lineages were overrepresented. In a subset of patients, this appeared to accompany the appearance of a B-lymphoid-like hierarchy. Together, our data reveal the emergence of apparent subtype-specific plasticity upon treatment and inform on potential novel therapeutic angles to target these cell populations.

2023-11-20 | GSE235308 | GEO

A longitudinal single-cell atlas of treatment response in pediatric AML (scRNA-Seq)

2023-11-20 | GSE235063 | GEO

Genome-wide mapping of histone H3 lysine 27 acetylation in acute myeloid leukemia

Project description:Somatic mutations are rare in pediatric AML (pAML), indicating alternate strategies are needed to identify new, pediatric AML-specific, druggable targets. We defined the enhancer landscape of 22 pAML patient samples and observed many known leukemia regulators are SE-associated in pAML. The retinoic acid receptor alpha (RARA) gene was differentially regulated in our cohort and present in all cyto/molecular subtypes tested, totaling 64% of the pAML samples. RARA SE-positive pAML cell lines and samples had higher RARA mRNA levels than RARA SE-negative samples and also were specifically sensitive to the synthetic RARA agonist tamibarotene in vitro, with halted proliferation and upregulated retinoid target genes. Tamibarotene prolonged survival and suppressed the leukemia burden of a RARA SE-positive pAML patient-derived xenograft (PDX) mouse model compared to a RARA SE-negative PDX. These data demonstrate the utility of leveraging chromatin regulation to identify new dependencies in pediatric AML and specifically lay the preclinical foundation for a tamibarotene trial in children with relapsed/refractory AML.

2021-08-01 | GSE155558 | GEO

Global gene expression of pediatric acute myeloid leukemia

Project description:Somatic mutations are rare in pediatric AML (pAML), indicating alternate strategies are needed to identify new, pediatric AML-specific, druggable targets. We defined the enhancer landscape of 22 pAML patient samples and observed many known leukemia regulators are SE-associated in pAML. We confirmed that the expression of several of these SE-associated genes correlated with gene expression by RNA-Seq. The retinoic acid receptor alpha (RARA) gene was differentially regulated in our cohort and present in all cyto/molecular subtypes tested, totaling 64% of the pAML samples. RARA SE-positive pAML cell lines and samples had higher RARA mRNA levels than RARA SE-negative samples and also were specifically sensitive to the synthetic RARA agonist tamibarotene in vitro, with halted proliferation and upregulated retinoid target genes. Tamibarotene prolonged survival and suppressed the leukemia burden of a RARA SE-positive pAML patient-derived xenograft (PDX) mouse model compared to a RARA SE-negative PDX. These data demonstrate the utility of leveraging chromatin regulation to identify new dependencies in pediatric AML and specifically lay the preclinical foundation for a tamibarotene trial in children with relapsed/refractory AML.

2021-08-01 | GSE176559 | GEO

Wnt/Ca2+/NFAT signaling maintains survival of Ph+ leukemia cells upon inhibition of Bcr-Abl

Project description:Although Bcr-Abl kinase inhibitors have proven effective in the treatment of chronic myeloid leukemia (CML), they generally fail to completely eradicate Bcr-Abl+ leukemia cells. To identify genes whose inhibition sensitizes Bcr-Abl+ leukemias to killing by Bcr-Abl inhibitors, we performed an RNAi-based synthetic lethal screen with imatinib in CML cells. This screen identified numerous components of a Wnt/Ca2+/NFAT signaling pathway. Antagonism of this pathway led to impaired NFAT activity, decreased cytokine production and enhanced sensitivity to Bcr-Abl inhibition. Furthermore, NFAT inhibition with cyclosporin A facilitated leukemia cell elimination by the Bcr-Abl inhibitor dasatinib and markedly improved survival in a mouse model of Bcr-Abl+ acute lymphoblastic leukemia (ALL). Targeting this pathway in combination with Bcr-Abl inhibition could improve treatment of Bcr-Abl+ leukemias. We utilized a genome-wide shRNA library in combination with microarray analysis to screen for gene targets in chronic myeloid leukemia cells that cooperate with imatinib.

2010-07-15 | E-GEOD-21499 | biostudies-arrayexpress

Transcriptome Analysis of Pediatric Acute Myeloid Leukemia

Project description:Transcriptome Analysis of Pediatric Acute Myeloid Leukemia

| PRJNA792548 | ENA

Comprehensive molecular and clinical characterization of NUP98 fusions in pediatric acute myeloid leukemia

Project description:Genome wide DNA methylation profiling of pediatric acute myeloid leukemia (AML) from diagnostic and relapsed specimens.

2021-12-15 | GSE190931 | GEO

Repurposing CD19-directed immunotherapies for pediatric t(8;21) acute myeloid leukemia

Project description:In contrast to patients with B cell precursor acute lymphoblastic leukemia (BCP-ALL), patients with acute myeloid leukemia (AML) have not yet benefited from recent advances in targeted immunotherapy. Repurposing immunotherapies that have been successfully used to target other hematological malignancies could, in case of a shared target antigen, represent a promising opportunity to expand the immunotherapeutic options for AML. Here, we evaluated the expression of CD19 in a large pediatric AML cohort, assessed the ex vivo AML killing efficacy of CD19-directed immunotherapies, and characterized the bone marrow immune microenvironment in pediatric AML, BCP-ALL, and non-leukemic controls. Out of 167 newly diagnosed de novo pediatric AML patients, 18 patients (11%) had CD19+ AML, with 61% carrying the translocation t(8;21)(q22;q22). Among CD19+ samples, we observed a continuum of CD19 expression levels on AML cells. In individuals exhibiting unimodal and high CD19 expression, the antigen was consistently present on nearly all CD34+CD38- and CD34+CD38+ subpopulations. In ex vivo AML-T cell co-cultures, blinatumomab demonstrated substantial AML killing, with an efficacy similar to BCP-ALL. In addition, CAR T cells could effectively eliminate CD19+ AML cells ex vivo. Furthermore, our immunogenomic assessment of the bone marrow immune microenvironment of newly diagnosed pediatric t(8;21) AML revealed that T- and NK cells had a less exhausted and senescent phenotype in comparison to pediatric BCP-ALL. Altogether, our study underscores the promise of CD19-directed immunotherapies for the treatment of pediatric CD19+ AML.

2024-08-08 | GSE270185 | GEO

Deep genomic characterisation of pediatric acute myeloid leukemia

Project description:Deep genomic characterisation of pediatric acute myeloid leukemia

| PRJNA923810 | ENA