Relapsed Acute Lymphoblastic Leukemia (ALL): Genomic Analysis in Pediatric Patients
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ABSTRACT:
PROVIDER: PRJNA311978 | ENA |
REPOSITORIES: ENA
Similar Datasets
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:Relapsed Acute Lymphoblastic Leukemia (ALL): Mutational Landscape
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Project description:Relapsed Acute Lymphoblastic Leukemia (ALL): Mutational Landscape
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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:Pediatric acute lymphoblastic leukemia (ALL) contains cytogenetically distinct subtypes that respond differently to cytotoxic drugs. Subtype classification can be also achieved through gene expression profiling. However, how to apply such classifiers to a single patient and correctly diagnose the disease subtype in an independent patient group has not been addressed. Furthermore, the underlying regulatory mechanisms responsible for the subtype-specific gene expression patterns are still largely unknown. Here, by combining three published microarray datasets (PMIDs: 12086872, 12730115, 17002788) on 535 Caucasian samples and generating a new dataset on 100 Chinese children ALL samples, we were able to 1) identify a 62-gene classifier with 97.6% accuracy from the Caucasian samples and validated it on the completely independent set of 100 Chinese samples, 2) to uncover potential regulatory networks of ALL subtypes. The classifier we identified was so far the only one that could be applied directly to a single sample and sustained validation in a large independent patient group. Our results also suggest that the etiology of ALL is largely the same among different ethnic groups, and that the transcription factor hubs in the predicted regulatory network might play important roles in regulating gene expression and development of ALL. A total of 100 Chinese pediatric acute lymphoblastic leukemia bone marrow (BM) samples were analyzed, together with five non-ALL BM samples as negative control (the five samples were combined to generate one control, see details in Li et al. Blood, 2009). The diagnosis of ALL was based on morphology, immunology, cytogenetic and molecular (MICM) classification. Cytogenetic ALL subtypes were identified experimentally by G-banding karyotype and multiplex nested RT-PCR. Among the 100 ALL patients, eleven relapsed within five years. All the samples, including those relapsed afterward, were from patients treated on BCH-2003 protocol and were extracted at their initial diagnosis. The five non-ALL BM samples were taken from the removed bones of patients who had plastic surgery for their bone deformity in Beijing Children’s Hospital. And the informed consent was obtained from parents, guardians, or patients (as appropriate). More details are available in Li et al. Gene expression-based classification and regulatory networks of pediatric acute lymphoblastic leukemia, Blood, 2009. We have generated these ALL and control samples to validate that a high accuracy subtype classifier that we identified could be applied directly to a single sample and sustained validation in a large independent patient group.
2009-08-19 | E-GEOD-17703 | biostudies-arrayexpress
Project description:<p>Although multi-agent combination chemotherapy is curative in a significant fraction of childhood acute lymphoblastic leukemia (ALL) patients, 20% of cases relapse and most die due to chemo-refractory disease. Here we used whole-exome and whole-genome sequencing to analyze the mutational landscape and pattern of clonal evolution at relapse in pediatric ALL cases. These analyses showed that ALL relapses originate from a common ancestral precursor clone of the diagnosis and relapsed populations and frequently harbor mutations implicated in chemotherapy resistance. RAS-MAPK pathway activating mutations in NRAS, KRAS and PTPN11 were present in 24/55 (44%) cases in our series. Notably, while some cases showed emergence of RAS mutant clones at relapse, in others, RAS mutant clones present at diagnosis were replaced by RAS wild type populations. Mechanistically, functional dissection of mouse and human wild type Kras and mutant Kras (Kras G12D) isogenic leukemia cells demonstrated induction of methotrexate resistance, but also improved response to vincristine, in mutant Kras- expressing lymphoblasts. These results identify chemotherapy driven selection as a central mechanism of leukemia clonal evolution and pave the road for the development of tailored personalized therapies for the treatment of relapsed ALL. </p>
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Project description:Array comparative genomic hybridization data for 372 diagnosis pediatric acute lymphoblastic leukemia samples.
2023-03-13 | GSE184692 | GEO
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: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
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