Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Remodeling of the immune microenvironment is linked to adverse outcome in pediatric T cell acute lymphoblastic leukemia

ABSTRACT: Remodeling of the immune microenvironment is linked to adverse outcome in pediatric T cell acute lymphoblastic leukemia

PROVIDER: PRJNA1043165 | ENA |

REPOSITORIES: ENA

ACCESS DATA

Json Xml

Similar Datasets

Remodeling of the immune microenvironment is linked to adverse outcome in pediatric T cell acute lymphoblastic leukemia

Project description:Changes in the immune microenvironment are frequent in cancers occurring in adult patients, yet our understanding of the pediatric cancer immune microenvironment and its clinical relevance is limited. We investigate the immune microenvironment in pediatric T cell acute lymphoblastic leukemia (T-ALL), using single-cell CITE-seq and immune repertoire analyses. We identify a T-ALL subgroup characterized by a remodeled immune microenvironment, which is associated with adverse clinical outcome in minimal residual disease low patients. This adverse immune landscape is dominated by the presence of a population of non-malignant CD4-CD8-TCRab T cells that interact with CXCL16 expressing non-classical monocytes. Leukemia cell intrinsic transcriptional rewiring in these patients is associated with activation of Rap1 signaling. Inhibiting Rap1 signaling results in increased sensitivity to the BCL2/BCL-XL inhibitor navitoclax. Our study provides insights into the immune microenvironment of pediatric hematologic malignancies, forming the basis for identifying novel (immuno)therapeutic targets and risk stratification for treatment.

2025-07-25 | GSE248287 | GEO

Gene based outcome prediction in pediatric T-cell acute lymphoblastic leukemia

Project description:RNA was extracted from the diagnostic bone marrow specimens of 50 T-cell acute lymphoblastic leukemia pediatric patients and analysed by Affymetrix microarray to model gene classifiers predictive of clinical outcome

2012-07-06 | E-MTAB-1205 | biostudies-arrayexpress

microRNA expression levels as predictors of outcome in pediateric acute lymphoblastic leukemia (ALL) patients

Project description:Expression levels of specific microRNAs were significantly associated with adverse clinical parameters of pediatric ALL patients and might serve as novel biomarkers for outcome, at diagnosis, in these patients.

2015-06-01 | GSE45839 | GEO

MicroRNAs characterize genetic diversity and drug resistance in pediatric acute lymphoblastic leukemia

Project description:MicroRNAs (miRNAs) regulate activity of protein-coding genes including those involved in hematopoietic cancers. The goal of the current study was to explore which miRNAs are unique for seven different subtypes of pediatric acute lymphoblastic leukemia (ALL). Therefore, the expression levels of 397 miRNAs (including novel miRNAs) were measured by quantitative RT-PCR in 81 pediatric leukemia cases and 17 normal hematopoietic control cases. Except for BCR-ABL-positive and B-other ALL, all major subtypes i.e. T-ALL, MLL-rearranged, TEL-AML1-positive, E2A-PBX1-positive and hyperdiploid ALL have unique miRNA-signatures that differ from each other and from those in healthy hematopoietic cells. Strikingly, the miRNA signature between TEL-AML1-positive and hyperdiploid cases partly overlapped, which suggests a common underlying biology. Moreover, aberrant downregulation of let-7b (~70-fold) in MLL-rearranged ALL was linked to upregulation of oncoprotein c-Myc (P<0.0001). Besides genetic aberrations, in vitro drug resistance predicts clinical outcome. Resistance to vincristine and daunorubicin was characterized by ~20-fold upregulation of miR-125b, miR-99a and miR-100 (P≤0.002). No discriminative miRNAs were found for prednisolone and only one miRNA was linked to L-asparaginase resistance. Finally we show that the expression levels of 14 miRNAs were --independently of subtype-- associated with clinical outcome in pediatric ALL. We conclude that genetic subtypes and drug resistant leukemic cells display characteristic miRNA signatures in pediatric ALL. Functional studies of discriminative and prognostic important miRNAs may provide new insights into the biology of disease. Experiment type: stem-loop real-time (RT) quantitative PCR (RT-qPCR)

2011-02-11 | GSE23024 | GEO

MicroRNA-sequencing of Brazilian pediatric acute lymphoblastic leukemia

Project description:MicroRNA-sequencing of the bone marrow samples from Brazilian pediatric patients with B-cell acute lymphoblastic leukemia (B-ALL) and T-cell acute lymphoblastic leukemia (T-ALL).

2022-04-13 | E-MTAB-11621 | biostudies-arrayexpress

aCGH of a pediatric acute lymphoblastic leukemia cohort

Project description:Array comparative genomic hybridization data for 372 diagnosis pediatric acute lymphoblastic leukemia samples.

2023-03-13 | GSE184692 | GEO

miRNA profiling of pediatric T cell lymphoblastic lymphoma

Project description:miRNA profiling has been performed on primary tumor samples collected at diagnosis from pediatric patients affected by T-cell lymphoblastic lymphoma.

2014-06-10 | GSE55846 | GEO

Persistence of targetable lesions, predicted therapy sensitivity and proteomes through disease evolution in pediatric acute lymphoblastic leukemia

Project description:This data set consists of pediatric acute lymphoblastic leukemia (ALL) primary bone marrow biopsies from the BC Children's Hospital BioBank, pediatric ALL cell lines, non-cancer bone marrow biopsies, and few ALL PDX. All files are DIA and searched by Spectronaut with a spectral library.

2023-01-05 | MSV000091012 | MassIVE

The genomic landscape of pediatric T-cell acute lymphoblastic leukemia reveals novel X-linked somatic mutations associated with apoptosis resistance. [RNA-Seq]

Project description:Background. T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive hematological malignancy with a dismal prognosis. It represents 15% of pediatric ALL and has a threefold higher incidence among males. T-cell transformation is a multi-step process involving cooperating events leading to altered T-cell signaling, proliferation, differentiation and survival. Many recurrent alterations have been identified and help define molecular subgroups of T-ALL, however the full range of events involved in driving transformation remain to be defined. Results. Using an integrative approach combining genomic and transcriptomic data, we performed comprehensive molecular characterization of 30 pediatric T-ALLs. We identified common T-ALL targets and confirmed the overall poor outcome of early immature cases. We also showed that deletion of the CDKN2A locus is associated with lower risk of relapse. In addition, we identified novel T-ALL drivers including a member of the spliceosome machinery U2AF1 as well as novel X-linked tumor suppressors MED12 and USP9X, that had never been associated to T-ALL before. Interestingly, almost 60% of these events were found in early immature cases which represented only 35% of the cohort. Functional validations further demonstrated the putative role of these novel T-ALL genes in driving transformation by demonstrating the aberrant splicing provoked by U2AF1 p.R35L and the protective effect against apoptosis of MED12 and USP9X repression. Conclusions. This study highlights the underlying genomic complexity of pediatric T-ALL, and the need for larger integrative studies to decipher the mechanisms that contribute to its various subtypes and provide opportunities to refine patient stratification and treatment.

2016-03-02 | GSE78785 | GEO

The genomic landscape of pediatric T-cell acute lymphoblastic leukemia reveals novel X-linked somatic mutations associated with apoptosis resistance. [Exome-Seq]

2016-03-02 | GSE78783 | GEO