Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

Transcription profiling of human 164 MDS, 202 AML and 69 non-leukemia bone marrow samples to develop a gene array prediction of AML transformation in MDSm subset of MILE study data

ABSTRACT: 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.

ORGANISM(S): Homo sapiens

SUBMITTER: Wei-Min Liu

PROVIDER: E-GEOD-15061 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Microarray-based classifiers and prognosis models identify subgroups with distinct clinical outcomes and high risk of AML transformation of myelodysplastic syndrome.

Mills Ken I KI Kohlmann Alexander A Williams P Mickey PM Wieczorek Lothar L Liu Wei-min WM Li Rachel R Wei Wen W Bowen David T DT Loeffler Helmut H Hernandez Jesus M JM Hofmann Wolf-Karsten WK Haferlach Torsten T

Blood 20090514 5

The diagnosis of myelodysplastic syndrome (MDS) currently relies primarily on the morphologic assessment of the patient's bone marrow and peripheral blood cells. Moreover, prognostic scoring systems rely on observer-dependent assessments of blast percentage and dysplasia. Gene expression profiling could enhance current diagnostic and prognostic systems by providing a set of standardized, objective gene signatures. Within the Microarray Innovations in LEukemia study, a diagnostic classification m ...[more]

PMID: 19443663

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Project description:Full Title: Multilineage Dysplasia (MLD) in AML correlates with MDS-related cytogenetic abnormalities and a prior history of MDS or MDS/MPN but has no independent prognostic relevance: A comparison of 408 cases classified as “AML not otherwise specified” or “AML with myelodysplasia-related changes” The WHO classification of acute myeloid leukemia (AML) is hierarchically structured and integrates genetic information, data on patients’ history, and multilineage dysplasia (MLD). The category “AML with MDS-related changes” (AML-MRC) is separated from AML not otherwise specified (AML-NOS) by the presence of either MLD, MDS-related cytogenetics or MDS history. To clarify whether MLD alone is clinically relevant, we analyzed 408 adult patients categorized as AML-MRC or AML-NOS. EFS (Median 13.8 months vs. 16.0 months) and 3-year-OS (45.8% vs. 53.9%) did not differ significantly between patients with MLD and without. However, MLD correlated with pre-existing MDS (p<0.001) and MDS-related cytogenetics (p=0.035). Patients with MLD as sole AML-MRC criterion (AML-MLD-sole; n=90) had less frequently FLT3-ITD (p=0.032), and a lower median age than AML-NOS (n=232), but EFS, OS, and WBC did not differ significantly. Contrarily, patients with AML-NOS plus AML-MLD-sole (n=323) versus patients with MDS history or MDS-related cytogenetics (n=85) had better EFS (16.9 vs. 10.7 months; p=0.005) and 3-year-OS (55.8% vs. 32.5%; p=0.001). Gene expression profiles were measured for a subset of 96 patients. Analysis of the expression data showed distinct clusters for AML-MLD-sole and AML-NOS versus AML with MDS-related cytogenetics or MDS history. Thus, MLD demonstrated no independent clinical impact, while cytogenetics and MDS history were of prognostic relevance. This data suggest modifications in a revised WHO proposal. All 96 bone marrow 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.

Dataset Information

Transcription profiling of human 164 MDS, 202 AML and 69 non-leukemia bone marrow samples to develop a gene array prediction of AML transformation in MDSm subset of MILE study data

Publications

Microarray-based classifiers and prognosis models identify subgroups with distinct clinical outcomes and high risk of AML transformation of myelodysplastic syndrome.

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