PCGP CBF RNASEQ - samples
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ABSTRACT:
PROVIDER: EGAD00001002530 | EGA |
REPOSITORIES: EGA
Similar Datasets
Project description:Additional files for "The Genomic Landscape of Core-Binding Factor Acute Myeloid Leukemias" (EGAS00001000349). This dataset includes the processed Excap data referenced in this paper.
| EGAD00001002667 | EGA
Project description:<p>Pediatric <i>de novo</i> acute myeloid leukemia (AML) is a heterogeneous disease that can be divided into clinically distinct subtypes based on the presence of specific chromosomal abnormalities or gene alterations. One of the best characterized subtypes of AML involves leukemias with alterations of the core-binding factor (CBF)-complex, which comprises the FAB subtypes M2 and M4Eo and associates with a favorable outcome. Patients with the AML M2 subtype harbor a translocation between chromosomes 8 and 21 [t(8;21)] that yields the chimeric fusion gene <i>RUNX1(AML1)-RUNX1T1(ETO)</i>, while patients with AML M4Eo express the chimeric fusion gene <i>CBFβ-SMMHC(MYH11)</i> as a result of an inversion/translocation event of chromosome 16 [inv(16)/t(16;16)]. In an effort to define the total complement of genetic changes in CBF-leukemia, we performed paired-end whole genome sequencing (WGS) on diagnostic leukemia blasts and matched germ line samples from 17 pediatric CBF-leukemia patients using the Illumina platform. Somatic alterations, including single nucleotide variations (SNVs) and structural variations (SVs), including insertions, deletions, inversions, and inter- and intra-chromosomal rearrangements, were detected using complementary analysis pipelines (Bambino, CREST and CONSERTING). Recurrent screening of identified mutations will be performed in a cohort of approximately 94 cases of CBF-leukemias.</p>
| phs000414 | dbGaP
Project description:St. Jude Children's Research Hospital - Washington University Pediatric Cancer Genome Project (PCGP): Whole Genome Sequencing of Core Binding Factor Acute Myeloid Leukemia
| PRJNA75321 | ENA
Project description:Gene expression profiling identifies distinct subclasses of core binding factor acute myeloid leukemia.
| PRJNA101847 | ENA
Project description:This dataset contains RNA-Seq files for the SJACT cohort associated with the paper "Genetic landscape of pediatric Adrenocortical Tumor". In this paper, we analyse 37 adrenocortical tumours (ACTs) by whole-genome, whole-exome and/or transcriptome sequencing.
| EGAD00001002680 | EGA
Project description:Core binding factor (CBF) leukemias, characterized by either inv(16)/t(16;16) or t(8;21), constitute acute myeloid leukemia (AML) subgroups with favorable prognosis. However, there exists substantial biological and clinical heterogeneity within these cytogenetic groups, which is not fully reflected by the current classification system. To improve the molecular characterization we profiled gene expression in a large series (n=93) of AML patients with CBF leukemia [inv(16) n=55, t(8;21) n=38]. By unsupervised hierarchical clustering we were able to define a subgroup of CBF cases (n=35) characterized by shorter overall survival times (P=0.03). While there was no obvious correlation with fusion gene transcript levels, FLT3 tyrosine kinase domain, KIT, and NRAS mutations, the newly defined inv(16)/t(8;21)-subgroup was associated with elevated white blood cell counts and FLT3 internal tandem duplications (P=0.011 and P=0.026, respectively). Supervised analyses of gene expression suggested alternative cooperating pathways leading to transformation. In the ?favorable? CBF leukemias anti-apoptotic mechanisms and deregulated mTOR-signaling, and in the newly defined ?unfavorable? subgroup aberrant MAPKinase-signaling and chemotherapy-resistance mechanisms might play a role. While the leukemogenic relevance of these signatures remains to be validated, their existence nevertheless supports a prognostically relevant biological basis for the heterogeneity observed in CBF leukemia.
2007-06-10 | E-SMDB-4056 | biostudies-arrayexpress
Project description:Chronic and acute myeloid leukemia (CML/AML) evade immune surveillance and induce immunosuppression, largely by upregulating Foxp3+ regulatory T cells (Treg). However, mechanisms that drive Treg in myeloid leukemias are largely unknown. Here, we show that leukemic (CML- and AML-derived) extracellular vesicles (EVs) drive human Treg, by de novo induction of Treg and by upregulating suppressive phenotype and activity of Treg. Rab27a-mediated EVs secretion contributed to Treg expansion, activity, and leukemic engraftment in vivo in a mouse model of CML-like disease. Leukemic EVs downregulated mTOR-S6 and upregulated STAT5 signaling in T cells, to upregulate Foxp3 and Treg activity, as well as evoked significant transcriptomic changes in Treg. By using high resolution 23-color spectral flow cytometry we identified 2 distinct, highly suppressive subsets of Treg expanded by leukemic EVs, characterized by elevated expression of tumor Treg markers CCR8, CCR4, TIGIT, CD39, CD30, TNFR2 and IL21R. Finally, we identified 4 1BBL/TNFSF9 protein in leukemic EVs. Deficiency of 4-1BBL in leukemic cells and EVs resulted in lower expression of CD30, TNFR2 and LAG-3 on Treg and thus weaker effector phenotype. Collectively, our data pinpoint leukemic extracellular vesicles as a significant factor that drives regulatory T cells and immunosuppression in myeloid leukemias. Our results suggest that targeting of Rab27a and EVs secretion may be a viable therapeutic option in myeloid leukemias, whereas detection of 4 1BBL containing EVs could be used as an early biomarker of immunosuppression and leukemia development/relapse
2022-02-16 | PXD027240 | Pride
Project description:Core binding factor (CBF) leukemias, characterized by translocations t(8;21) or inv(16)/t(16;16) targeting the core binding factor, constitute acute myeloid leukemia (AML) subgroups with favorable prognosis. However, about 40% of patients relapse, and the current classification system does not fully reflect this clinical heterogeneity. Previously, gene expression profiling (GEP) revealed two distinct CBF leukemia subgroups displaying significant outcome differences and identified apoptotic signaling, MAPKinase signaling and chemotherapy-resistance mechanisms among the most significant differentially regulated pathways. We now tested different inhibitors of the respective pathways in a cell line model (six cell lines reflecting the CBF subgroup specific gene expression alterations), and found apoptotic signaling to be differentiating between the CBF subgroup models. In accordance, primary samples from newly diagnosed CBF AML patients (n=23) also showed differential sensitivity to in vitro treatment with a Smac mimetic such as BV6, an antagonist of inhibitor of apoptosis (IAP) proteins , and ABT-737, a BCL2 inhibitor. Furthermore, GEP revealed the BV6 resistant cases to resemble the previously identified unfavorable CBF subgroup. Thus, our current findings show deregulated IAP expression and apoptotic signaling to differentiate clinically relevant CBF subgroups, which were independent of known molecular markers, thereby providing a starting point for novel therapeutic approaches. All samples were obtained from untreated patients at the time of diagnosis. Cells used for microarray analysis were collected from the purified fraction of mononuclear cells after Ficoll density centrifugation. Routine diagnostic algorithms, including the characterization of molecular markers are performed.
2011-06-11 | E-GEOD-29883 | biostudies-arrayexpress
Project description:Long non-coding RNAs (lncRNAs) and miRNAs have emerged as crucial regulators of gene expression and cell fate decisions. Here we present an integrated analysis of the ncRNA-transcriptome of purified human hematopoietic stem cells (HSCs) and their differentiated progenies, including granulocytes, monocytes, T-cells, NK-cells, B-cells, megakaryocytes and erythroid precursors, which we correlated with the ncRNA expression profile of 48 pediatric AML samples to establish a core lncRNA stem cell signature in AML.Linear (PCA) and nonlinear (t-SNE) dimensionality reduction of 46 pediatric AML samples including Down syndrome AMKL, core-binding factor AMLs (inv[16] or t[8;21]) and MLL-rearranged leukemias mapped most samples to a space between HSCs and differentiated cells together with the myeloid progenitors. A subset of AML-samples mapped closely to healthy HSCs, including most of the DS-AMKLs and MLL-AMLs. Following the incorporation of acute myeloid leukemia (AML) samples into the landscape, we further uncover prognostically relevant ncRNA stem cell signatures shared between AML blasts and healthy hematopoietic stem cells.
2017-05-31 | GSE98697 | GEO