Ena-DATASET-U938-16-05-2016-13:29:03:177-146 - samples
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ABSTRACT:
PROVIDER: EGAD00001002118 | EGA |
REPOSITORIES: EGA
Similar Datasets
Project description:Raw data (fastq files) from targeted resequencing of AML patients at diagnosis
| EGAD00001002117 | EGA
Project description:Raw data (fastq files) from whole exome sequencing of AML patients (paired diagnosis and complete remission samples)
| EGAD00001002116 | EGA
Project description:Acute myeloid leukemia (AML) with inv(16) is typically associated to a favourable prognosis. However, up to 40% of patients will eventually experience disease relapse. Herein, we dissected the transcriptomic profile of AML with inv(16) to identify potential prognostic markers and devise novel therapeutic vulnerabilities. Sequencing data from 222 diagnostic samples, including 44 relapse/refractory patients, revealed the presence of a median of 1 concomitant additional mutation, cooperating with inv(16) in leukemogenesis. Notably, the mutational landscape at diagnosis did not significantly differ between patients experiencing primary induction failure or relapse when compared to the rest of the cohort, except for an increase in the mutational burden in the relapse/refractory group. RNA-Seq of unpaired diagnostic and relapse) samples allowed the identification of oxidative phosphorylation (OXPHOS) as one of the most significantly downregulated pathways at relapse. Considering that OXPHOS could be targeted by Venetoclax/Azacitidine combination, we explored its biological effects on ME-1 inv(16) cell-line, but there was no additional advantage in terms of proliferation suppression over Azacitidine alone. To enhance Venetoclax efficacy, we tested the in vitro effects of Metformin as a potential drug able to enhance chemosensitivity of AML cells by inhibiting the mitochondrial transfer. By challenging ME-1 with this combination, we observed a significant synergistic interaction at least similar to that of Venetoclax/Azacitidine. In conclusion, the study of transcriptomic features of inv(16) at relapse unveiled OXPHOS as a potential target in this subset. The use of specific metabolic-oriented and synthetic lethal approaches (e.g., Venetoclax/Metformin) provided a rationale for its future clinical use.
2026-06-30 | GSE254098 | GEO
Project description:Genome-wide profiling of Copy Number Alterations (CNA) and Loss of Heterozygosity (LOH), gene expression and resequencing of pediatric AML. This study characterizes the CNA and LOH in a representative cross-section through subtypes of pediatric AML. Affymetrix SNP arrays were performed according to the manufacturer's directions on DNA extracted from cryopreserved diagnostic bone marrow or peripheral blood samples. 111 pediatric AML samples were studied using either Affymetrix 100K + 500K 5.0 SNP arrays, 65 of the samples had paired germ line material. The supplemental file 'GSE15732_AML_175_SNP_Xba_signal.txt' contains the raw signals generated by dChip without normalization. The CNA and LOH data can be found in the Supplemental Information of the associated manuscript.
2010-01-03 | E-GEOD-15732 | biostudies-arrayexpress
Project description:Genome-wide profiling of Copy Number Alterations (CNA) and Loss of Heterozygosity (LOH), gene expression and resequencing of pediatric AML. This study characterizes the CNA and LOH in a representative cross-section through subtypes of pediatric AML. Affymetrix SNP arrays were performed according to the manufacturer's directions on DNA extracted from cryopreserved diagnostic bone marrow or peripheral blood samples. 111 pediatric AML samples were studied using either Affymetrix 100K + 500K 5.0 SNP arrays, 65 of the samples had paired germ line material. The supplemental file 'GSE15714_AML_175_SNP_Hind_signal.txt' contains the raw signals generated by dChip without normalization. The CNA and LOH data can be found in the Supplemental Information of the associated manuscript.
2010-01-03 | E-GEOD-15714 | biostudies-arrayexpress
Project description:Genome-wide profiling of Copy Number Alterations (CNA) and Loss of Heterozygosity (LOH), gene expression and resequencing of pediatric AML. This study characterizes the CNA and LOH in a representative cross-section through subtypes of pediatric AML. Affymetrix SNP arrays were performed according to the manufacturer's directions on DNA extracted from cryopreserved diagnostic bone marrow or peripheral blood samples. 111 pediatric AML samples were studied using either Affymetrix 100K + 500K 5.0 SNP arrays, 65 of the samples had paired germ line material. The supplemental files 'GSE15730_AML_175_SNP_Nsp_signal.txt' and 'GSE15730_AML_176_SNP_Nsp_signal.txt' contain the raw signals generated by dChip without normalization. The CNA and LOH data can be found in the Supplemental Information of the associated manuscript.
2010-04-13 | E-GEOD-15730 | biostudies-arrayexpress
Project description:Genome-wide profiling of Copy Number Alterations (CNA) and Loss of Heterozygosity (LOH), gene expression and resequencing of pediatric AML. This study characterizes the CNA and LOH in a representative cross-section through subtypes of pediatric AML. Affymetrix SNP arrays were performed according to the manufacturer's directions on DNA extracted from cryopreserved diagnostic bone marrow or peripheral blood samples. 111 pediatric AML samples were studied using either Affymetrix 100K + 500K 5.0 SNP arrays, 65 of the samples had paired germ line material. The supplemental files 'GSE15731_AML_175_SNP_Sty_signal.txt' and 'GSE15731_AML_176_SNP_Sty_signal.txt' contain the raw signals generated by dChip without normalization. The CNA and LOH data can be found in the Supplemental Information of the associated manuscript.
2010-01-03 | E-GEOD-15731 | biostudies-arrayexpress
Project description:Study of AMl clonal phylogeny. Fastq files from targeted resequencing and from exome sequencing from AML patients at diagnosis, complete remission or relapse time.
| EGAS00001001779 | EGA
Project description:Mutations in the nucleophosmin 1 (NPM1) gene are considered as a founder event in the pathogenesis of acute myeloid leukemia (AML). To address the role of clonal evolution in relapsed NPM1 mutated (NPM1mut) AML, we applied high-resolution genome-wide single-nucleotide polymorphism (SNP) array profiling to detect copy number alterations (CNA) and uniparental disomies (UPD) and performed comprehensive gene mutation screening in 53 paired bone marrow/peripheral blood samples obtained at diagnosis and relapse. At diagnosis, 15 aberrations (CNAs, n=10; UPDs, n=5) were identified in 13 patients (25%), whereas at relapse 56 genomic alterations (CNAs, n=46; UPDs, n=10) were detected in 29 patients (55%) indicating an increase in genomic complexity. Recurrent aberrations acquired at relapse included deletions affecting tumor suppressor genes [ETV6 (n=3), TP53 (n=2), NF1 (n=2), WT1 (n=3), FHIT (n=2)] and homozygous FLT3 mutations acquired via UPD13q (n=7). DNMT3A mutations (DNMT3Amut) showed the highest stability (97%). Persistence of DNMT3Amut in 5 patients who lost NPM1mut at relapse suggests that DNMT3Amut may precede NPM1mut in AML pathogenesis. Of note, all relapse samples shared at least one genetic aberration with the matched primary AML sample implying common ancestral clones. In conclusion, our study reveals novel insights into clonal evolution in NPM1mut AML. Bone marrow or peripheral blood samples from diagnosis, remission and relapse of 53 NPM1 mutated AML patient were analyzed on the Affymetrix Genome-Wide Human SNP 6.0 Array. Raw data (CEL-Files) were transformed to genotyping files (CHP) with Genotyping Console Version 4.2 from Affymetrix. Bioinformatic evaluation of CNAs was performed using dChipSNP and circular binary segmentation .
2013-05-30 | E-GEOD-46951 | biostudies-arrayexpress
Project description:Thlaspi arvense 13-16 Resequencing
| PRJNA1239692 | ENA