Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

NOTCH1 fusion genes in pediatric T-cell lymphoblastic lymphoma hallmark a common high-risk subgroup with blood TARC levels as possible biomarker

ABSTRACT: T-cell lymphoblastic lymphoma (T-LBL) is a common pediatric malignancy accounting for approximately 20% of the non-Hodgkin lymphomas during childhood. Survival rates of T-LBL are ~80%, but outcome after relapse is dismal, with salvage rates reaching only ~15. Considering the extremely poor prognosis after relapse and absence of clinically relevant high-risk genetics, there is an urgent need for the identification of molecular risk factors and new prognostic biomarkers in T-LBL, as well as identification of new therapeutic strategies. In this study we present a novel entity of high-risk pediatric T-LBL patients characterized by previously unknown NOTCH1 gene fusions and highly elevated blood TARC levels

PROVIDER: EGAS00001007703 | EGA |

REPOSITORIES: EGA

ACCESS DATA

Json Xml

Similar Datasets

PMCDS000ABP - samples

Project description:T-cell lymphoblastic lymphoma (T-LBL) is a common pediatric malignancy accounting for approximately 20% of the non-Hodgkin lymphomas during childhood. Survival rates of T-LBL are ~80%, but outcome after relapse is dismal, with salvage rates reaching only ~15. Considering the extremely poor prognosis after relapse and absence of clinically relevant high-risk genetics, there is an urgent need for the identification of molecular risk factors and new prognostic biomarkers in T-LBL, as well as identification of new therapeutic strategies. In this study we present a novel entity of high-risk pediatric T-LBL patients characterized by previously unknown NOTCH1 gene fusions and highly elevated blood TARC levels

| EGAD00001015255 | EGA

IKZF1 deletions predict relapse in uniformly treated pediatric precursor B-ALL

Project description:Relapse is the most common cause of treatment failure in pediatric acute lymphoblastic leukemia (ALL) and is often difficult to predict. To explore the prognostic impact of recurrent DNA copy number abnormalities on relapse, we performed high-resolution genomic profiling of 34 paired diagnosis-relapse ALL samples. Recurrent lesions detected at diagnosis, including PAX5, CDKN2A, and EBF1, were frequently absent at relapse, indicating that they represent secondary events that may be absent in the relapse-prone therapy-resistant progenitor cell. In contrast, deletions and nonsense mutations in IKZF1 (IKAROS), were highly enriched and consistently preserved at the time of relapse. A targeted copy number screen in an unselected cohort of 131 precursor B-ALL cases, enrolled in the dexamethasone-based Dutch Childhood Oncology Group treatment protocol ALL9, revealed that IKZF1 deletions are significantly associated with poor relapse-free and overall survival rates. Separate analysis of ALL9-treatment subgroups revealed that non-high-risk patients with IKZF1 deletions exhibited a ~12-fold higher relative relapse rate than those without IKZF1 deletions. Consequently, IKZF1 deletion status allowed the prospective identification of 53% of the relapse-prone non-high-risk-classified patients within this subgroup and, therefore, serves as one of the strongest predictors of relapse at the time of diagnosis with high potential for future risk stratification. Affymetrix NspI 250k array data of 34 paired diagnosis and relapse samples of pediatric ALL. From 13 patients a complete remission sample was available. Four cases had 2 relapses.

2010-03-01 | GSE20353 | GEO

A miRNA-based signature associated to relapse in pediatric t(8;21)RUNX1-RUNX1T1

Project description:We performed genome wide miRNA expression analysis to investigate the ability of miRNAs in predicting leukemia relapse from 33 t(8;21) pediatric AMLs at diagnosis divided into a training and a validation cohort. COX regression analysis and ROC curves were used to identify a powerful miRNA signature able to predict relapse in t(8;21) AML patients. miRNA profiling showed that patients with high- or low- risk of relapse had different expression profiles. We support the role of microRNAs in modulating the prognosis of t(8;21)-AML and the use of a miRNA expression signature at diagnosis to better define standard risk cases in pediatric AML.

2017-09-14 | GSE97135 | GEO

Mutational patterns and clonal evolution from diagnosis to relapse in pediatric acute lymphoblastic leukemia

Project description:Despite high survival rates in pediatric acute lymphoblastic leukemia (ALL), relapse remains a leading cause of cancer-related death in children. Many patients suffer from adverse drug effects during treatment and other complications later in life, and would benefit from improved relapse prediction at diagnosis. We performed whole genome sequencing of samples collected at diagnosis, relapse(s) and remission from 29 Nordic patients with pediatric ALL. Somatic mutations were called using individually matched remission samples as controls, and allelic expression of the mutations in the ALL cells was assessed using RNA-sequencing. These analyses identified 29 previously known ALL driver genes, of which nine genes carried recurrent protein-coding mutations in our sample set, and 20 mutated driver genes occurred in individual samples. We detected putative non-coding mutations in regulatory regions of seven additional genes that have not been described previously in ALL. We observed an increased burden of somatic mutations at relapse. Cluster analysis of hundreds of somatic mutations per sample revealed three distinct evolutionary trajectories during ALL progression. In an “ancestral clone trajectory”, the major cell clone at relapse originated from a founder clone that was not detectable at diagnosis. In a “rising diagnostic clone trajectory”, a minor cell clone at diagnosis expanded to form the major cell clone at relapse. In a “persistent diagnostic clone trajectory”, the major cell clone at diagnosis persisted during treatment until relapse. The evolutionary trajectories provide insight into the mutational mechanisms leading relapse in ALL and could offer biomarkers for improved risk prediction in individual patients.

2021-08-11 | GSE163634 | GEO

BCL-2 levels do not predict azathioprine treatment response in inflammatory bowel disease, but inhibition induces lymphocyte apoptosis and ameliorates colitis in mice.

Project description:Background: Inducing apoptosis of autoreactive lymphocytes is part of the therapeutic strategy for Crohn’s disease (CD) patients. Failure to respond to medical therapies upon inflammatory bowel disease could result from insufficient apoptosis. To date there are no useful molecular factors for the prediction of clinical relapse. Study Aims: Characterization of the BCL-2 family-related risk of therapy resistance and verifying its usefulness as parameter for the prediction of clinical relapse could be helpful in deciding which medical therapy to recommend. The project is directly targeted to develop rapidly therapeutic improvement for patients with IBD. A long-term goal is the development of new therapeutic options for the treatment of IBD via a physiologic homeostasis and turnover of lymphocytes. Study Design: We propose to characterize the BCL-2 family-related risk of therapy resistance and its usefulness as parameter for the prediction of clinical relapse upon medical therapy. Samples will be used for next generation sequencing, qPCR, WB, immunohistochemistry and immunofluorescence. The hypothesis is considered confirmed if expression of BCL-2 family members in human peripheral blood is significantly changed between patient groups and correlates with the number of lymphocyte subpopulations.

2018-05-14 | E-MTAB-6739 | biostudies-arrayexpress

DNA methylation adds prognostic value to minimal residual disease status in pediatric T-cell acute lymphoblastic leukemia

Project description:Background: Despite increased knowledge about genetic aberrations in pediatric T-cell acute lymphoblastic leukemia (T-ALL), no clinically feasible treatment-stratifying marker exists at diagnosis. Instead patients are enrolled in intensive induction therapies with substantial side effects. In modern protocols, therapy response is monitored by minimal residual disease (MRD) analysis, and used for post-induction risk group stratification. DNA methylation profiling is a candidate for subtype discrimination at diagnosis and we investigated its role as a prognostic marker in pediatric T-ALL. Procedure: Sixty-five diagnostic T-ALL samples from Nordic pediatric patients treated according to the NOPHO-ALL2008 protocol were analyzed by HumMeth450K genome wide DNA methylation arrays. Methylation status was analyzed in relation to clinical data and early T-cell precursor (ETP) phenotype. Results: Two distinct CpG Island Methylator Phenotype (CIMP) groups were identified. Patients with a CIMP negative profile had an inferior response to treatment compared to CIMP positive patients (3-year cumulative incidence of relapse (CIR3y) rate: 29% vs. 6%, p=0.01). Most importantly, CIMP classification at diagnosis allowed subgrouping of high risk T-ALL patients (MRD â?¥0.1% at day 29) into two groups with significant differences in outcome (CIR3y rates: CIMP negative 50% vs CIMP positive 12%; p=0.02). These groups did not differ regarding ETP-phenotype, but the CIMP negative group was younger (p=0.02) and had higher white blood cell count at diagnosis (p=0.004) compared with the CIMP positive group. Conclusions: CIMP classification at diagnosis in combination with MRD during induction therapy is a strong candidate for further risk classification and could confer important information in treatment decision-making. Bisulphite converted DNA from T-ALL samples were hybridised to the Illumina Infinium 450k Human Methylation Beadchip

2016-03-30 | E-GEOD-69954 | biostudies-arrayexpress

Global gene expression analysis of CD10+/CD19+ pre B lymphoblasts from bone marrow and peripheral blood of B-ALL patients

Project description:Acute lymphoblastic leukemia (ALL) is the most frequent childhood cancer. Mexico City has one of the highest incidences in the world, with pediatric patients showing a poor response to conventional therapy, low survival rates and high relapse rates. We performed a global gene expression profile of pre B lymphoblasts from bone marrow (BM) and peripheral blood (PB) samples from B-ALL patients to find the upregulated and downregulated genes in both cell populations in the context of this childhood cancer.

2022-04-27 | GSE168593 | GEO

Integrated Genomic Analysis of Relapsed Childhood Acute Lymphoblastic Leukemia reveals therapeutic strategies

Project description:This SuperSeries is composed of the following subset Series: GSE28460: Expression data from ALL diagnosis and relapse pediatric acute lymphoblastic leukemia cases GSE28461: Promoter methylation data from ALL diagnosis and relapse pediatric acute lymphoblastic leukemia cases Refer to individual Series

2011-09-22 | E-GEOD-28462 | biostudies-arrayexpress

Gene expression profiling of pediatric myelodysplastic syndrome (MDS) characterizes disease subtype and time to progression into acute myeloid leukemia (AML)

Project description:Identification of relevant subgroups in childhood MDS patients by gene expression analysis and gene involve in progression into AML Class comparison between different subgroups of pediatric MDS (class risk, classification subtype)

2012-02-29 | E-GEOD-29326 | biostudies-arrayexpress

Immune Escape after Allogeneic Hematopoietic Cell Transplantation in Pediatric Patients with Acute Myeloid Leukemia

Project description:Although allogeneic hematopoietic cell transplantation (allo-HCT) is curative for high-risk pediatric acute myeloid leukemia (AML), disease relapse remains the primary cause of post-transplant mortality. To identify pressures imposed by allo-HCT on AML cells that escape the graft-versus-leukemia effect, we evaluated immune signatures in bone marrow samples from four pediatric patients using a multimodal single-cell approach. Downregulation of MHC class II (MHC-II) expression observed at post-transplant relapse was most profound in progenitor-like blasts and was accompanied by correlative changes in transcriptional regulation. Dysfunction of activated NK cells and CD8+ T cell subsets at the time of relapse was evidenced by the loss of IFN-γ response, TNF-a signaling via NF-kB, and IL-2/STAT5 signaling. Clonotype analysis of post-transplant relapse samples revealed expansion of dysfunctional T cells and enrichment of T regulatory and T helper cells. Using novel computational methods, our results illustrate a diverse immune-related transcriptional signature in post-transplantation relapses not previously reported in pediatric AML.

2023-06-26 | GSE207104 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data