Homo sapiens
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA167028 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Abnormal replication timing has been observed in cancer but no study has comprehensively evaluated this misregulation. We generated genome-wide replication timing profiles for pediatric leukemias from 17 patients and 3 cell lines, as well as normal B and T cells. Non-leukemic EBV-transformed lymphoblastoid cell lines displayed highly stable replication timing profiles that were more similar to normal T cells than to leukemias. Leukemias were more similar to each other than to B and T cells but were considerably more heterogeneous than non-leukemic controls. Some differences were patient-specific while others were found in all leukemic samples, potentially representing early epigenetic events. Differences encompassed large segments of chromosomes and included genes implicated in other types of cancer. Remarkably, differences that distinguished leukemias aligned in register to the boundaries of developmentally regulated replication timing domains that distinguish normal cell types. Most changes did not coincide with copy number variation or translocations. However, many of the changes that were associated with translocations in some leukemias were also shared between all leukemic samples independent of the genetic lesion, suggesting that they precede and possibly predispose chromosomes to the translocation. Altogether, our results identify sites of abnormal developmental control of DNA replication in cancer that reveal the significance of replication timing boundaries to chromosome structure and function and support the replication domain model of replication timing regulation. They also open new avenues of investigation into the chromosomal basis of cancer and provide a potential novel source of epigenetic cancer biomarkers. Four karyotypically normal B-lymphoblastoid cell types with two replicates each, one peripheral T-lymphoblast replicate, 3 leukemic cell lines with 1-3 replicates each, 17 patient samples with 1-3 replicates each (total of 40 individual replicates)
2012-05-16 | E-GEOD-37987 | biostudies-arrayexpress
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
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
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
Project description:Abnormal replication timing has been observed in cancer but no study has comprehensively evaluated this misregulation. We generated genome-wide replication timing profiles for pediatric leukemias from 17 patients and 3 cell lines, as well as normal B and T cells. Non-leukemic EBV-transformed lymphoblastoid cell lines displayed highly stable replication timing profiles that were more similar to normal T cells than to leukemias. Leukemias were more similar to each other than to B and T cells but were considerably more heterogeneous than non-leukemic controls. Some differences were patient-specific while others were found in all leukemic samples, potentially representing early epigenetic events. Differences encompassed large segments of chromosomes and included genes implicated in other types of cancer. Remarkably, differences that distinguished leukemias aligned in register to the boundaries of developmentally regulated replication timing domains that distinguish normal cell types. Most changes did not coincide with copy number variation or translocations. However, many of the changes that were associated with translocations in some leukemias were also shared between all leukemic samples independent of the genetic lesion, suggesting that they precede and possibly predispose chromosomes to the translocation. Altogether, our results identify sites of abnormal developmental control of DNA replication in cancer that reveal the significance of replication timing boundaries to chromosome structure and function and support the replication domain model of replication timing regulation. They also open new avenues of investigation into the chromosomal basis of cancer and provide a potential novel source of epigenetic cancer biomarkers.
2012-05-16 | GSE37987 | GEO
Project description:In multicellular organisms, developmental changes to replication timing occur in 400- 800 kb domains across half the genome. While clear examples of epigenetic control of replication timing have been described, a role for DNA sequence in mammalian replication timing has not been substantiated. To assess the role of DNA sequences in directing these changes, we profiled replication timing in mice carrying a genetically rearranged Human Chromosome 21 [Hsa21]. In two distinct mouse cell types, Hsa21 sequences maintained human-specific replication timing, except at points of Hsa21 rearrangement. Changes in replication timing at rearrangements extended up to 900 kb and consistently reconciled with the wild-type replication pattern at developmental boundaries of replication-timing domains. Our results demonstrate DNA sequencedriven regulation of Hsa21 replication timing during development and provide evidence that mammalian chromosomes consist of multiple independent units of replication timing regulation.
2012-06-05 | GSE38472 | GEO
Project description:In multicellular organisms, developmental changes to replication timing occur in 400- 800 kb domains across half the genome. While clear examples of epigenetic control of replication timing have been described, a role for DNA sequence in mammalian replication timing has not been substantiated. To assess the role of DNA sequences in directing these changes, we profiled replication timing in mice carrying a genetically rearranged Human Chromosome 21 [Hsa21]. In two distinct mouse cell types, Hsa21 sequences maintained human-specific replication timing, except at points of Hsa21 rearrangement. Changes in replication timing at rearrangements extended up to 900 kb and consistently reconciled with the wild-type replication pattern at developmental boundaries of replication-timing domains. Our results demonstrate DNA sequencedriven regulation of Hsa21 replication timing during development and provide evidence that mammalian chromosomes consist of multiple independent units of replication timing regulation. Profile comparison of fibroblast and T-cell cultures from trans-chromosomic mice and human and mouse controls.
2012-06-04 | E-GEOD-38472 | biostudies-arrayexpress
Project description:The development of a clinically relevant xenograft model of pediatric acute lymphoblastic leukemia, using a 4-drug treatment regimen designed to mimic pediatric remission induction therapy. Relapse and acquired drug resistance in T-cell acute lymphoblastic leukemia (T-ALL) remains a significant clinical problem. This study was designed to establish a preclinical model of resistance to induction therapy in childhood T-ALL to examine the emergence of drug resistance and identify novel therapies. We performed transcription profiling by array of human CD45-positive human lymphocytes from patients with acute pediatric lymphoblastic leukemia, and from xenografted NOD/SCID mice treated with vincristine, daunorubicin, dexamethasone and L-asparagine. Several different treatment regimes were used in this study (VLXD, VLXDR, VLXD2, VXL and VLXD2-ALL31) and are summarised in the protocols associated with this submission.
2013-11-01 | E-MEXP-3916 | biostudies-arrayexpress
Project description:Genome-wide assessment of gene expression in primary acute lymphoblastic leukemia cells was performed to identify genomic determinants of MTXâs antileukemic effects. Reduction of circulating leukemia cells after in vivo methotrexate treatment served as a measure MTX's antileukemic effects. Experiment Overall Design: Gene expression in diagnostic primary acute lymphoblastic leukemia cells from bone marrow of 161 pediatric patients
2008-04-06 | E-GEOD-10255 | biostudies-arrayexpress
Project description:B-cell precursor acute lymphoblastic leukemia (BCP-ALL) cells reside in the bone marrow microenvironment, where they are protected against chemotherapeutic agents. Mesenchymal stromal cells (MSCs) are key components of this supporting framework. The present study aimed to unravel whether MSCs derived from pediatric BCP-ALL patients (leukemic MSCs) differ from MSCs derived from healthy pediatric donors (control-MSCs). Therefore, we studied their gene expression profiles after 40 hours of co-culture with primary B-cell precursor acute lymphoblastic leukemia cells. MSCs were sorted using fluorescence-activated cell sorting (FACS).
2020-07-13 | GSE101454 | GEO