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Protein Array Screening of Myelodysplastic Syndromes I

ABSTRACT: In a two-stage study we investigated levels of Immunoglobulin G (IgG) reactivity in plasma from Myelodysplastic Syndrome (MDS) and Acute Myeloid Leukemia (AML) post MDS patients (59 and 16 cases respectively) as compared to healthy cohort (34). In Stage I we utilized high-throughput protein arrays (23 232 total signals, in duplicate) to identify proteins of high-interest. In Stage II we designed new protein arrays (352 total signals, in duplicate) to further focus on 25 of the proteins from Stage I and expanded to a larger cohort, including both male and female samples (161 MDS and 43 AML patients; 112 healthy controls). Stage I resulted in 35 proteins displaying increased IgG reactivity in patients as compared to the healthy controls (P< 4.3 x10-07, Bonferroni Corrected P<0.01). This protein subset included 14 proteins associated with cancer, 12 with apoptosis, and 3 with the NFAT Regulation canonical pathway. Using the focused arrays we performed a classification of MDS patients and healthy controls. Stage II subsequently identified a high-interest focused set of 3 proteins, namely AKT3, FCGR3A and ARL8B displaying aberrant increased reactivity in patient subgroups, in concordance with Stage I. Autoantibody reactivity against specific proteins provides complementary information to other known molecular signatures for MDS and may enhance our capabilities for detecting and classifying MDS. In the study presented here, MDS patients were classified into Stable, Transforming or AML post MDS (L) classes retrospectively. The different patients were compared to a healthy cohort to assess increased autoantibody reactivity to specific patients as opposed to healthy groups

ORGANISM(S): Homo sapiens unidentified

PROVIDER: GSE48153 | GEO | 2013/11/21

SECONDARY ACCESSION(S): PRJNA209054

REPOSITORIES: GEO

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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.

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Protein Array Screening of Myelodysplastic Syndromes I

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