Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Molecular characterization of very early relapsed childhood ALL

ABSTRACT: Purpose: In childhood acute lymphoblastic leukemia (ALL), approximately 25% of patients suffer from relapse. In recurrent disease, despite intensified therapy, overall cure rates of 40% remain unsatisfactory and survival rates are particularly poor in certain subgroups. The probability of long-term survival after relapse is predicted from well-established prognostic factors, i. e. time and site of relapse, immunophenotype and minimal residual disease. However, the underlying biological determinants of these prognostic factors remain poorly understood. Results: We show here that patients with very early relapse of ALL are characterized by a distinctive gene expression pattern. We identified a set of 83 genes differentially expressed in very early relapsed ALL compared to late relapsed disease. The vast majority of genes was up-regulated and many were late cell cycle genes with a function in mitosis. In addition, samples from patients with very early relapse showed a significant increase in the percentage of S and G/2M phase cells and this correlated well with the expression level of cell cycle genes. Conclusions: Very early relapse of ALL is characterized by an increased proliferative capacity of leukemic blasts and up-regulated mitotic genes. The latter suggests that novel drugs, targeting late cell cycle proteins, might be beneficial for these patients that typically face a dismal prognosis. Keywords: disease state analysis

ORGANISM(S): Homo sapiens

PROVIDER: GSE4698 | GEO | 2006/09/27

SECONDARY ACCESSION(S): PRJNA96749

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Similar Datasets

Transcription profiling of human ALL samples from very early relapsed childhood patients

Project description:Purpose: In childhood acute lymphoblastic leukemia (ALL), approximately 25% of patients suffer from relapse. In recurrent disease, despite intensified therapy, overall cure rates of 40% remain unsatisfactory and survival rates are particularly poor in certain subgroups. The probability of long-term survival after relapse is predicted from well-established prognostic factors, i. e. time and site of relapse, immunophenotype and minimal residual disease. However, the underlying biological determinants of these prognostic factors remain poorly understood. Results: We show here that patients with very early relapse of ALL are characterized by a distinctive gene expression pattern. We identified a set of 83 genes differentially expressed in very early relapsed ALL compared to late relapsed disease. The vast majority of genes was up-regulated and many were late cell cycle genes with a function in mitosis. In addition, samples from patients with very early relapse showed a significant increase in the percentage of S and G/2M phase cells and this correlated well with the expression level of cell cycle genes. Conclusions: Very early relapse of ALL is characterized by an increased proliferative capacity of leukemic blasts and up-regulated mitotic genes. The latter suggests that novel drugs, targeting late cell cycle proteins, might be beneficial for these patients that typically face a dismal prognosis. Experiment Overall Design: We performed gene expression profiling on 60 prospectively collected samples of children with first relapse of acute lymphoblastic leukemia enrolled on the relapse trial ALL-REZ BFM 2002 of the Berlin-Frankfurt-Muenster study group.

2008-06-13 | E-GEOD-4698 | biostudies-arrayexpress

Relapsed diffuse large B-cell lymphoma present different genomic patterns of alterations between early and late relapses

Project description:Despite major advances in first-line treatment, a significant proportion of patients with diffuse large B-cell lymphoma (DLBCL) will experience treatment failure. Time of relapse is a major prognostic parameter in this context, with a particularly poor prognosis for early relapse. Our purpose was to determine genomic alterations associated with early-relapsed (ER) and late-relapsed (LR) DLBCLs, using high resolution array-based comparative genomic hybridization and integrating structural abnormalities and gene expression of 39 samples from the Collaborative Trial in Relapsed Aggressive Lymphoma (CORAL) study. ER and LR DLBCLs present a similar landscape of large copy number variations (CNVs), with an average 14.89 and 16.11 CNVs per sample, respectively (p=0.81). Deletions of CDKN2A/B (28%) and IBTK (23%) were frequent events in relapsed DLBCLs. We identified 56 protein-coding genes and 25 long non-coding RNAs with significantly differential CNVs distribution between ER and LR DLBCLs with a false discovery rate < 0.05. In ER DLBCLs, genetic abnormalities were related to regulation of transcription, cell cycle and apoptosis, with duplications of histone H1T (31%), deletions of DIABLO (26%), PTMS (21%) and CK2B (15%). In LR DLBCLs, genetic aberrations were related to immune response, with alterations of IgHV (40%), IgKV (15%), and deletions of B2M (20%) and CD58 (10%), regulation of cell proliferation, with duplications of HES1 and DVL3 (25% and 20%, respectively) and regulation of transcription, with MTERF4 deletions (20%). This study provides new insights into the genetic abnormalities in relapsed DLBCLs. Dysregulation of cell cycle, apoptosis and gene transcription may indicate targeted therapy.

2016-09-26 | GSE73791 | GEO

Diagnosis-relapse in ALL

Project description:Almost a quarter of pediatric patients with Acute Lymphoblastic Leukemia (ALL) suffer from relapses. The biological mechanisms underlying therapy response and development of relapses have remained unclear. In an attempt to better understand this phenomenon, we have analyzed 41 matched diagnosis relapse pairs of ALL patients using genomeâ??wide expression arrays (82 arrays) on purified leukemic cells. In roughly half of the patients very few differences between diagnosis and relapse samples were found (â??stable groupâ??), suggesting that mostly extra-leukemic factors (e.g., drug distribution, drug metabolism, compliance) contributed to the relapse. Therefore, we focused our further analysis on 20 samples with clear differences in gene expression (â??skewed groupâ??), reasoning that these would allow us to better study the biological mechanisms underlying relapsed ALL. After finding the differences between diagnosis and relapse pairs in this group, we identified four major gene clusters corresponding to several pathways associated with changes in cell cycle, DNA replication, recombination and repair, as well as B cell developmental genes. We also identified cancer genes commonly associated with colon carcinomas and ubiquitination to be upregulated in relapsed ALL. Thus, about half of relapses are due to selection or emergence of a clone with deregulated expression of a genes involved in pathways that regulate B cell signaling, development, cell cycle, cellular division and replication. The study contains 41 pairs of samples taken from patients at diagnosis and relapse (a total of 82 arrays).

2010-03-23 | E-GEOD-18497 | biostudies-arrayexpress

microRNA alterations associated to clinical response in advanced stage ovarian cancer patients (training set)

Project description:In order to investigate miRNA alterations associated to early relapse in ovarian cancer patients, we analyzed miRNA expression profile in a training set of 55 surgical specimens including 30 early relapsing and 25 late relapsing patients. Patients were selected on the basis of residual disease after primary surgery and time to relapse (TTR) after front-line chemotherapy. For training set, a selection of the outliers concerning TTR was made: as early relapsing were defined optimally debulked (OD) patients with a TTR< 12 months and sub-optimally debulked (SOD) patients with TTR< 6 months; late relapsing were defined OD patients with TTR> 36 months and SOD patients with TTR> 12 months. Clinical codes: Histotype: according to International Federation of Gynecological and Obstetrics guidelines Stage: according to International Federation of Gynecological and Obstetrics guidelines Grading: according to International Federation of Gynecological and Obstetrics guidelines Debulking: NED: not evident disease; mRD: minimal residual disease; GRD: gross residual disease Therapy code: P: Platinum without taxanes; PT: Platinum/paclitaxel End Point: Early: relapse whithin 12 and 6 months from the end of therapy for optimally (NED+ mRD) and sub-optimally (GRD) debulked patients respectively. Late: median time to relapse 48 and 34 months from the end of therapy for optimally and sub-optimally debulked patients respectively.

2012-03-09 | E-GEOD-25202 | biostudies-arrayexpress

microRNA alterations associated to clinical response in advanced stage ovarian cancer patients (test set)

Project description:In order to investigate miRNA alterations associated to early relapse in ovarian cancer patietns, we analyzed miRNA expression profile in a test set of 30 surgical specimens including 13 early and 17 late relapsing patients. Samples included in test set were obtained from formalin-fixed paraffin-embedded (FFPE) specimens. Patients were selected on the basis of residual disease after primary surgery and time to relapse (TTR) after front-line chemotherapy. For the test set, a selection of the outliers concerning TTR was made: 12 months from the end of therapy was the TTR selected to define early (<12 months) or late (>12 months) relapsing patients. Clinical codes: Histotype: according to International Federation of Gynecological and Obstetrics guidelines Stage: according to International Federation of Gynecological and Obstetrics guidelines Grading: according to International Federation of Gynecological and Obstetrics guidelines Debulking: NED: not evident disease; mRD: minimal residual disease; GRD: gross residual disease Therapy code: P: Platinum without taxanes; PT: Platinum/paclitaxel End Point: Early: relapse whithin 12 and 6 months from the end of therapy for optimally (NED+ mRD) and sub-optimally (GRD) debulked patients respectively. Late: median time to relapse 48 and 34 months from the end of therapy for optimally and sub-optimally debulked patients respectively.

2012-03-09 | E-GEOD-25203 | biostudies-arrayexpress

Analysis of non-relapsed and relapsed adult type granulosa cell tumors suggests stable transcriptomes during tumor progression

Project description:Adult-type granulosa cell tumor (AGCT) is a rare ovarian malignancy characterized by slow growth and hormonal activity. The prognosis of AGCT is generally favorable, but one-third of patients with low-stage disease experience a late relapse, and over half of them die of AGCT. To identify markers that would distinguish patients at risk for relapse, we performed Lexogen QuantSeq 3’ mRNA sequencing on formalin-fixed paraffin-embedded, archival AGCT tissue samples tested positive for the pathognomonic FOXL2-mutation. We compared the transcriptomic profiles of 14 non-relapsed archival primary AGCTs (follow-up time 17-26 years after diagnosis) with 13 relapsed primary AGCTs (follow-up time 1.7-18 years) and eight relapsed tumors (follow-up time 2.8-18.9 years). Non-relapsed and relapsed primary AGCTs had similar transcriptomic profiles. In relapsed tumors three genes were differentially expressed: plasmalemma vesicle associated protein (PLVAP) was upregulated (p=0.01), whereas argininosuccinate synthase 1 (ASS1) (p=0.01) and perilipin 4 (PLIN4) (p=0.02) were downregulated. PLVAP upregulation was validated using tissue microarray RNA in situ hybridization. In our patient cohort with extremely long follow-up, we observed similar gene expression patterns in both primary AGCT groups suggesting that relapse is not driven by transcriptomic changes. These results reinforce earlier findings that molecular markers do not predict AGCT behavior or risk of relapse.

2022-03-23 | GSE190942 | GEO

Genomics of Relapsed Small Cell Lung Cancer Progression

Project description:<p>Small cell lung cancer (SCLC) accounts for nearly 15% of all patients with lung cancer. Though the response to initial therapy is favorable in many patients, a majority of patients go on to develop recurrent disease which is very difficult to treat. The response rates to chemotherapy are very low and most patients succumb to relapsed SCLC within a few months. Virtually no progress has been made in the treatment of SCLC in the last three decades. In order to better understand the molecular alterations in relapsed SCLC, we have generated exome and RNA sequence from normal, primary tumor and relapse tissues of SCLC patients.</p>

| phs001049 | dbGaP

Epigenomic Evolution of Diffuse Large B-cell Relapse

Project description:Here we characterize an association between disease progression and DNA methylation in Diffuse Large B cell Lymphoma (DLBCL). By profiling genome-wide DNA methylation at single base-pair resolution in thirteen DLBCL diagnosis-relapse sample pairs, we show DLBCL patients exhibit heterogeneous evolution of tumor methylomes during relapse. We identify differentially methylated regulatory elements and determine a relapse–associated methylation signature converging on key pathways such as transforming growth factor beta (TGF-beta) receptor activity. We also observe decreased intra-tumor methylation heterogeneity from diagnosis to relapsed tumor samples. Relapse-free patients display lower intra-tumor methylation heterogeneity at diagnosis compared to relapsed patients in an independent validation cohort. Furthermore, intra-tumor methylation heterogeneity is predictive of time to relapse. Therefore, we propose that epigenomic heterogeneity may support or drive the relapse phenotype and can be used to predict DLBCL relapse. Using ERRBS, we profiled genome-wide DNA methylation patterns of non-relapse DLBCL tumor samples at diagnosis, relaspe DLBCL patient samples at diagnosis and relaspe.

2015-04-14 | E-GEOD-66329 | biostudies-arrayexpress

Homozygous BCMA gene deletion in response to anti-BCMA CAR T cells in a patient with Multiple Myeloma

Project description:Chimeric antigen receptor T-cells (CAR-T) targeting B-cell-maturating-antigen (TNRFSF17, BCMA) show unprecedented overall response rates of up to 100% in heavily pretreated relapsed-refractory Multiple Myeloma (RRMM). However, the efficiency of the treatment is hindered by the rapid emergence of tumor-intrinsic mechanisms of resistance. We herein describe a patient with RRMM and extramedullary disease (EMD) who underwent Idecabtagene vicleucel BCMA CAR-T therapy. The patient rapidly achieved very good partial response including full resolution of EMD, but aggressively relapsed 5 months after CAR T cell infusion. Single cell RNA sequencing and immunohistochemistry on the re-emerging tumor cells demonstrated loss of target expression on mRNA and protein levels, and whole genome sequencing revealed the homozygous deletion of Chr 16p1313, including the BCMA locus. Clonal heterogeneity of BCMA could be observed in 32 RRMM patients from our institution. In three of them heterozygous deletion of BCMA could be confirmed, with none of them having underwent prior anti-BCMA therapy. Thus, our report not only provides first evidence of BCMA loss as the underlying mechanism of disease relapse following BCMA targeted immunotherapy in MM. It furthermore identifies a subset of patients at risk to develop biallelic BCMA inactivation thus linking genomic instability in MM to relapse from targeted immunotherapies.

2020-12-30 | GSE143317 | GEO

Diagnosis-relapse in ALL

Project description:Almost a quarter of pediatric patients with Acute Lymphoblastic Leukemia (ALL) suffer from relapses. The biological mechanisms underlying therapy response and development of relapses have remained unclear. In an attempt to better understand this phenomenon, we have analyzed 41 matched diagnosis relapse pairs of ALL patients using genome–wide expression arrays (82 arrays) on purified leukemic cells. In roughly half of the patients very few differences between diagnosis and relapse samples were found (“stable group”), suggesting that mostly extra-leukemic factors (e.g., drug distribution, drug metabolism, compliance) contributed to the relapse. Therefore, we focused our further analysis on 20 samples with clear differences in gene expression (“skewed group”), reasoning that these would allow us to better study the biological mechanisms underlying relapsed ALL. After finding the differences between diagnosis and relapse pairs in this group, we identified four major gene clusters corresponding to several pathways associated with changes in cell cycle, DNA replication, recombination and repair, as well as B cell developmental genes. We also identified cancer genes commonly associated with colon carcinomas and ubiquitination to be upregulated in relapsed ALL. Thus, about half of relapses are due to selection or emergence of a clone with deregulated expression of a genes involved in pathways that regulate B cell signaling, development, cell cycle, cellular division and replication.

2010-03-10 | GSE18497 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

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