Project description:An International Multi-Center Study to Define the Clinical Utility of Microarray–Based Gene Expression Profiling in the Diagnosis and Sub-classification of Leukemia (MILE Study) Established in 2005, the MILE (Microarray Innovations in LEukemia) study research program included 11 participating centers in three continents. This cohort of n=1,152 samples represents data on the retrospective whole-genome analysis phase. This dataset is part of the MILE Study (Microarray Innovations In LEukemia) program, headed by the European Leukemia Network (ELN) and sponsored by Roche Molecular Systems, Inc.
Project description:An International Multi-Center Study to Define the Clinical Utility of Microarray–Based Gene Expression Profiling in the Diagnosis and Sub-classification of Leukemia (MILE Study) Established in 2005, the MILE (Microarray Innovations in LEukemia) study research program included 11 participating centers in three continents. This cohort of n=2,096 samples represents data on the retrospective whole-genome analysis phase. This dataset is part of the MILE Study (Microarray Innovations In LEukemia) program, headed by the European Leukemia Network (ELN) and sponsored by Roche Molecular Systems, Inc.
2009-09-30 | GSE13159 | GEO
Project description:Microarray Innovations in LEukemia (MILE) study
Project description:An International Multi-Center Study to Define the Clinical Utility of MicroarrayâBased Gene Expression Profiling in the Diagnosis and Sub-classification of Leukemia (MILE Study) Established in 2005, the MILE (Microarray Innovations in LEukemia) study research program included 11 participating centers in three continents. This cohort of n=1,152 samples represents data on the retrospective whole-genome analysis phase. This dataset is part of the MILE Study (Microarray Innovations In LEukemia) program, headed by the European Leukemia Network (ELN) and sponsored by Roche Molecular Systems, Inc. 1,152 blood or bone marrow samples of acute and chronic leukemia patients were hybridized to the Roche AmpliChip Leukemia Custom Microarray
Project description:An International Multi-Center Study to Define the Clinical Utility of Microarray–Based Gene Expression Profiling in the Diagnosis and Sub-classification of Leukemia (MILE Study) Established in 2005, the MILE (Microarray Innovations in LEukemia) study research program included 11 participating centers in three continents. This cohort of n=2,096 samples represents data on the retrospective whole-genome analysis phase. This dataset is part of the MILE Study (Microarray Innovations In LEukemia) program, headed by the European Leukemia Network (ELN) and sponsored by Roche Molecular Systems, Inc. 2096 blood or bone marrow samples of acute and chronic leukemia patients were hybridized to Affymetrix HG-U133 Plus 2.0 GeneChips.
Project description:Microarray-based classifiers and prognosis models identify subgroups with distinct clinical outcomes and high risk of AML transformation of myelodysplastic syndrome (MDS); An array-based Diagnostic Classifier (DC) model, developed for and evaluated during the MILE study, correctly identified ~50% of the unfractionated MDS specimens submitted to the study; predictions for the other samples were split between “none-of-the-targets” classes and AML signatures, but this distinction also reflected clinical outcome in terms of time to AML transformation. Furthermore, an improved Prognostic Classifier (PC) model was developed that correlated with both time to AML transformation and overall survival. Experiment Overall Design: 164 MDS, 202 AML and 69 non-leukemia bone marrow samples were hybridized to Affymetrix HG-U133 Plus 2.0 GeneChips. Experiment Overall Design: This dataset is a subset of the MILE Study (Microarray Innovations In LEukemia) program, headed by the European Leukemia Network (ELN) and sponsored by Roche Molecular Systems, Inc.
Project description:An international standardization program towards the application of gene expression profiling in routine leukaemia diagnostics: The MILE study pre-phase. A total of 11 laboratories from three continents performed 204 analyses using a whole-genome expression microarray. In an effort to standardize the microarray procedure, each participating centre was equipped with identical hardware, software, and reagents. Designated study operators received intensive individual training on the sample preparation protocol. Experiment Overall Design: This study is part of the MILE Study (Microarray Innovations In LEukemia) program, headed by the European Leukaemia Network (ELN) and sponsored by Roche Molecular Systems, Inc. Experiment Overall Design: Each laboratory prepared two separate cell line total RNA samples, as well as three replicate leukaemia patient lysates in two distinct project stages: (i) a five-day course of protocol training, and (ii) independent proficiency testing. Experiment Overall Design: Using unsupervised, supervised, and r² correlation analyses we demonstrated that microarray analysis can be performed not only with remarkably high intra-laboratory reproducibility but also with comparable quality and reliability between eleven distinct laboratories.
Project description:Kynureninase is a member of a large family of catalytically diverse but structurally homologous pyridoxal 5'-phosphate (PLP) dependent enzymes known as the aspartate aminotransferase superfamily or alpha-family. The Homo sapiens and other eukaryotic constitutive kynureninases preferentially catalyze the hydrolytic cleavage of 3-hydroxy-l-kynurenine to produce 3-hydroxyanthranilate and l-alanine, while l-kynurenine is the substrate of many prokaryotic inducible kynureninases. The human enzyme was cloned with an N-terminal hexahistidine tag, expressed, and purified from a bacterial expression system using Ni metal ion affinity chromatography. Kinetic characterization of the recombinant enzyme reveals classic Michaelis-Menten behavior, with a Km of 28.3 +/- 1.9 microM and a specific activity of 1.75 micromol min-1 mg-1 for 3-hydroxy-dl-kynurenine. Crystals of recombinant kynureninase that diffracted to 2.0 A were obtained, and the atomic structure of the PLP-bound holoenzyme was determined by molecular replacement using the Pseudomonas fluorescens kynureninase structure (PDB entry 1qz9) as the phasing model. A structural superposition with the P. fluorescens kynureninase revealed that these two structures resemble the "open" and "closed" conformations of aspartate aminotransferase. The comparison illustrates the dynamic nature of these proteins' small domains and reveals a role for Arg-434 similar to its role in other AAT alpha-family members. Docking of 3-hydroxy-l-kynurenine into the human kynureninase active site suggests that Asn-333 and His-102 are involved in substrate binding and molecular discrimination between inducible and constitutive kynureninase substrates.