Gene expression profile of pediatric AML
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ABSTRACT:
ORGANISM(S): Homo sapiens
SUBMITTER: Hitoshi Ichikawa
PROVIDER: E-GEOD-35784 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
Similar Datasets
Project description:Gene expression data were obtained from 130 pediatric AML patients who were enrolled on the AML99 study conducted by the Japanese Childhood AML Cooperative Study Group.
2013-04-01 | GSE35784 | GEO
Project description:MicroRNAs (miRNAs) play a pivotal role in the regulation of hematopoiesis and development of leukemia. Great interest emerged in modulating miRNA expression for therapeutic purposes. In order to identify miRNAs, which specifically suppress leukemic growth of AML with t(8;21), inv(16) or MLL-rearrangement by inducing differentiation, we conducted a miRNA expression profiling in a cohort of 90 cytogenetically characterized, de novo pediatric AML cases. Four miRNAs, specifically downregulated in MLL-rearranged, t(8;21) or inv(16) AMLs, were characterized by their tumor suppressive properties in cell lines representing those respective cytogenetic groups. Among those, forced expression of miR-9 reduced leukemic growth and induced monocytic differentiation of t(8;21) AML cell lines in vitro and in vivo. The tumor suppressive functions of miR-9 were specifically restricted to AML cell lines and primary leukemic blasts with t(8;21). On the other hand, these functions were not evident in AML blasts from patients with MLL-rearrangements. We showed that miR-9 exerts its effects through the cooperation with let-7 to repress the oncogenic LIN28B/HMGA2 axis. Thus, miR-9 is a tumor suppressor-miR which acts in a stringent cell context-dependent manner. In order to identify miRNAs, which specifically suppress leukemic growth of AML with t(8;21) (n=21), inv(16) (n=17) or MLL-rearrangement (n=35) by inducing differentiation, we conducted a miRNA expression profiling in a cohort of 90 cytogenetically characterized, de novo pediatric AML cases, which also included 12 t(15;17) and 5 t(7;12) samples.
2014-01-01 | E-GEOD-52541 | biostudies-arrayexpress
Project description:Acute Myeloid Leukemia (AML) is a heterogeneous disease with several recurrent cytogenetic abnormalities. Despite genomics and transcriptomics profiling efforts to understand AML’s heterogeneity, studies focused on the proteomic profiles associated with pediatric AML cytogenetic features remain limited. Furthermore, the majority of biological functions within cells are operated by proteins (i.e., enzymes) and most drugs target the proteome rather than the genome or transcriptome, thus, highlighting the significance of studying proteomics.
2023-09-26 | PXD043982 | Pride
Project description:Despite improvement of current treatment strategies and novel targeted drugs, relapse and treatment resistance determine the major cause of death for acute myeloid leukemia (AML) patients. To identify the underlying molecular characteristics, numerous studies have been aimed to decipher the genomic- and transcriptomic landscape of AML. Nevertheless, further molecular changes allowing malignant cells to escape treatment are yet to be elucidated. Mass spectrometry is a powerful tool enabling detailed insights into proteomic changes that could explain AML relapse and resistance. Here, we investigated AML samples from 47 adult and 22 pediatric patients at serial time-points during disease progression using high resolution isoelectric focusing liquid chromatography mass spectrometry. We show that the proteomic profile at relapse is enriched for mitochondrial ribosomal proteins and subunits of the respiratory chain complex, indicative of reprogrammed energy metabolism from diagnosis to relapse. Further, higher levels of granzymes and lower levels of the anti-inflammatory protein CR1/CD35 suggest an inflammatory signature promoting disease progression. Finally, through a proteogenomic approach, we detected novel peptides, which present a promising repertoire in the search for biomarkers and tumor-specific druggable targets. Altogether, this study highlights the importance of proteomic studies in holistic approaches to improve treatment and survival of AML patients.
2023-01-09 | PXD031107 | Pride
Project description:Acute myeloid leukemia (AML) is the most common form of acute leukemia in adults and the second most common form of leukemia in children. Multiple lncRNAs participate in normal and may be implicated in malignant hematopoiesis associated with blood cell cancers, such as leukemia. Currently, the expression profile of lncRNAs in pediatric AML is unclear. In this study, we evaluated the lncRNA expression profile in the tissue of three pediatric AML patients with lncRNA microarray techniques. In order to gain insight into the function of targets of lncRNAs, GO term and KEGG pathway annotation were applied to the target gene pool. qPCR was performed to evaluate the expression patterns of dys-regulated lncRNAs. Bone marrow specimens were obtained at the time of diagnosis during routine clinical assessment of 3 pediatric patients with AML, who presented at the Department of Hematology and Oncology, Children's Hospital of Soochow University between 2000 and 2011. Additionally, bone marrow samples from 3 healthy donors were analyzed as controls. Human LncRNA Array analysis was performed by KangChen Bio-tech, Shanghai P.R. China. Total RNA from each sample was quantified by the NanoDrop ND-1000 and RNA integrity was assessed by standard denaturing agarose gel electrophoresis. For microarray analysis, Agilent Array platform was employed. The sample preparation and microarray hybridization were performed based on the manufacturerâs standard protocols with minor modifications. Briefly, mRNA was purified from total RNA after removal of rRNA (mRNA-ONLY⢠Eukaryotic mRNA Isolation Kit, Epicentre). Then, each sample was amplified and transcribed into fluorescent cRNA along the entire length of the transcripts without 3â bias utilizing a random priming method. The labeled cRNAs were hybridized onto the Human LncRNA Array v2.0 (8 x 60K, Arraystar). After having washed the slides, the arrays were scanned by the Agilent Scanner G2505C. Agilent Feature Extraction software (version 11.0.1.1) was used to analyze acquired array images. Quantile normalization and subsequent data processing were performed using the GeneSpring GX v12.0 software package (Agilent Technologies). After quantile normalization of the raw data, LncRNAs and mRNAs that at least 4 out of 6 samples have flags in Present or Marginal (âAll Targets Valueâ) were chosen for further data analysis. Differentially expressed LncRNAs and mRNAs with statistical significance between the two groups were identified through Volcano Plot filtering. Pathway analysis and GO analysis were applied to determine the roles of these differentially expressed mRNAs played in these biological pathways or GO terms. Finally, Hierarchical Clustering was performed to show the distinguishable LncRNAs and mRNAs expression pattern among samples.
2015-12-31 | E-GEOD-65263 | biostudies-arrayexpress
Project description:Contemporary treatment of pediatric acute myeloid leukemia (AML) requires the assignment of patients to specific risk groups. To explore whether expression profiling of leukemic blasts could accurately distinguish between the known risk groups of AML, we analyzed 130 pediatric and 20 adult AML diagnostic bone marrow or peripheral blood samples using the Affymetrix U133A microarray. Class discriminating genes were identified for each of the major prognostic subtypes of pediatric AML, including t(15;17)[PML-RARalpha], t(8;21)[AML1-ETO], inv(16) [CBFbeta-MYH11], MLL chimeric fusion genes, and cases classified as FAB-M7. When subsets of these genes were used in supervised learning algorithms, an overall classification accuracy of more than 93% was achieved. Moreover, we were able to use the expression signatures generated from the pediatric samples to accurately classify adult de novo AMLs with the same genetic lesions. The class discriminating genes also provided novel insights into the molecular pathobiology of these leukemias. Finally, using a combined pediatric data set of 130 AMLs and 137 acute lymphoblastic leukemias, we identified an expression signature for cases with MLL chimeric fusion genes irrespective of lineage. Surprisingly, AMLs containing partial tandem duplications of MLL failed to cluster with MLL chimeric fusion gene cases, suggesting a significant difference in their underlying mechanism of transformation. All the gene expression arrays are available through http://www.stjuderesearch.org/site/data/AML1/ in the original study (PMID:15226186). To study the RAS gene expression in the human AML patients, a total of 104 AML cases with known KRAS and NRAS status (including 72 gene expression arrays in the original study and 32 additional arrays acquired later on), as well as 4 CD34+ normal bone marrow cases deposited in GEO GSE33315, were including in this depository. Gene expression profiling was performed on 104 single diagnosis tumor samples and 4 CD34+ normal bone marrow samples
2013-07-02 | E-GEOD-43176 | biostudies-arrayexpress
Project description:The pretreatment karyotype of leukemic blasts is currently the key determinant in therapy decision-making in acute myeloid leukemia (AML). However, approximately fifty percent of AML patients, often carrying a normal karyotype, are currently unclassifiable based these established methods. Gene expression profiling has proven to be valuable for risk stratification of AML. This is a repository of 662 adult AML cases characterized on gene expression microarrays and used for different studies investigating the mechanisms underlying leukemogenesis. Bone marrow aspirates or peripheral blood samples of three independent representative cohorts of de novo AML patients, comprising 277, 256 and 129 cases respectively, were collected at diagnosis. Gene expression profiling was performed on 662 adult AML patients who have been treated according to Dutch-Belgian Hemato-Oncology Cooperative Group and the Swiss Group for Clinical Cancer Research (HOVON/SAKK) AML-04, -04A, -29, -32, -42, -42A, -43 and -92 protocols (available at http://www.hovon.nl). All patients provided written informed consent in accordance with the Declaration of Helsinki, and the study was approved by all participating institutional review boards. Blast cell purification and RNA isolation were performed as previously described (Valk et al., Prognostically Useful Gene-Expression Profiles in Acute Myeloid Leukemia, New England Journal of Medicine, 2004).
2016-06-23 | E-MTAB-3444 | biostudies-arrayexpress
Project description:Analysis of gene expression change after galectin-9 stimulation in primary CD34+TIM-3+ AML cells Total RNA obtained from purified CD34+TIM-3+ primary AML cells with or without recombinant human galectin-9 stimulation (20hrs) was subjected to transcriptome analysis
2014-10-10 | E-GEOD-62223 | biostudies-arrayexpress
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2013-02-12 | E-GEOD-41646 | biostudies-arrayexpress
Project description:In the present study, we investigated whether, and to what extent, P2Rs and their ligands are involved in the regulation of AML cells. Our findings show that AML blasts express several receptors belonging to the P2X and P2Y family. Although different samples respond differently to ATP and UTP stimulation (reflecting the variability intrinsic to the group of acute myeloid leukemias), all the tested samples appear to be responsive to purinergic signalling, as demonstrated by intracellular calcium mobilization. GEP analysis demonstrated that ATP induced the expression of cell cycle inhibitors and negative modulators of cell motility, such as inhibitors of GTPase activity. On the contrary, ATP inhibits the expression cell-cycle related genes (cyclins and CDKs), activators of cell motility (Rho GTPases regulators, matrix degradation enzyme and cytoskeleton proteins) and adhesion molecules involved in homing and engraftment. Blast cells obtained from 12 AML patients (3 M0/M1; 3 M2; 3 M4; and 3 M5) were cultured for 24 h with or without 1 mM ATP. Total RNA from 106 ATP-treated and untreated cells was extracted to study variation of gene expression profile induced by ATP treatment in leukemic cells.
2012-02-25 | E-GEOD-30903 | biostudies-arrayexpress