Patients with cytogenetically normal acute myeloid leukemia (CN-AML) show heterogeneous treatment outcomes. We used gene expression profiling to develop a gene signature that predicts overall survival (OS) in CN-AML. Based on data from 163 patients treated in the German AMLCG 1999 trial and analyzed on oligonucleotide microarrays, we used supervised principal component analysis to identify 86 probe sets (representing 66 different genes) which correlated with OS, and defined a prognostic score based on this signature. When applied to an independent cohort of 79 CN-AML patients, this continuous score remained a significant predictor for OS (hazard ratio [HR], 1.85; P=0.002), EFS (HR, 1.73; P=0.001), and RFS (HR, 1.76; P=0.025). It kept its prognostic value in multivariate analyses adjusting for age, FLT3 ITD and NPM1 status. In a validation cohort of 64 CN-AML patients treated on CALGB study 9621, the score also predicted OS (HR, 4.11; P<0.001), EFS (HR, 2.90; P<0.001), and RFS (HR, 3.14, P<0.001) and retained its significance in a multivariate model for OS. In summary, we present a novel gene expression signature that offers additional prognostic information for patients with CN-AML.
An 86-probe-set gene-expression signature predicts survival in cytogenetically normal acute myeloid leukemia.
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View SamplesThe cure rate for childhood ALL has improved considerably in part because therapy is routinely tailored to the predicted risk of relapse. Various clinical and laboratory variables are used in current risk-stratification schemes, but many children who fail therapy lack adverse prognostic factors at initial diagnosis. Using gene expression analysis, we have identified genes and pathways in a NCI high-risk childhood B-precursor ALL cohort at diagnosis that may play a role in early blast regression as correlated with the Day 7 marrow status. We have also identified a 47-probeset signature (representing 41 unique genes) that was predictive of long term outcome in our dataset as well as three large independent datasets of childhood ALL treated on different protocols.
Gene expression signatures predictive of early response and outcome in high-risk childhood acute lymphoblastic leukemia: A Children's Oncology Group Study [corrected].
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Phenotypic and genomic analysis of multiple myeloma minimal residual disease tumor cells: a new model to understand chemoresistance.
Specimen part, Disease
View SamplesPersistence of chemoresistant minimal residual disease (MRD) plasma cells (PCs) relates to inferior survival in multiple myeloma (MM). MRD PCs are therefore a minor clone able to recapitulate the initial tumor burden at relapse and accordingly, its characterization may represent a unique model to understand chemoresistance; unfortunately, the MRD clone has never been biologically investigated. Here, we compared the antigenic profile of MRD vs. diagnostic clonal PCs in 40 elderly MM patients enrolled in the GEM2010MAS65 study, and showed that the MRD clone is enriched by cells over-expressing integrins (CD11a/CD11c/CD29/CD49d/CD49e), chemokine receptors (CXCR4) and adhesion molecules (CD44/CD54). Genetic profiling of MRD vs. diagnostic PCs showed identical copy number alterations (CNAs) in 3/8 cases, 2 patients with linear acquisition of additional CNAs in MRD clonal PCs, and 3 cases with variable acquisition and loss of CNAs over time. The MRD clone showed significant downregulation of genes particularly related to protein processing in endoplasmic reticulum, as well as novel deregulated genes such as ALCAM that is prognostically relevant in MM and identifies chemoresistant PCs in vitro. Together, we show that therapy-induced clonal selection is already present at the MRD stage, in which chemoresistant PCs show a specific phenotypic signature that may result from the persistence of clones with different genetic and gene expression profiles.
Phenotypic and genomic analysis of multiple myeloma minimal residual disease tumor cells: a new model to understand chemoresistance.
Specimen part, Disease
View SamplesThe goal of the study was to characterize the molecular signatures of CD8 T cell subpopulations sorted from HIV+ lymph nodes and HIV- tonsils. We compared the transcriptome profiles of follicular and non -foliccular CD8 T cells (sorted based on the surface expression fo CCR7 and CXCR5, chemokine receptors that govern the intratissue trafficking of T cells). This is the first study addressing this question. We found several genes differentially expressed in these two CD8 T cell populations. Our pathway analysis revealed that several pathways related to costimulation/activation as well as to beta-catenin pathway were differentially expressed in these two CD8 t cell populations too. Overall design: CD8 T cell populations were sorted and whole transcriptome analysis was performed using an Illumina machine
Follicular CD8 T cells accumulate in HIV infection and can kill infected cells in vitro via bispecific antibodies.
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View SamplesThis SuperSeries is composed of the SubSeries listed below.
Integration of copy number and transcriptomics provides risk stratification in prostate cancer: A discovery and validation cohort study.
Specimen part, Disease, Subject
View SamplesBackground
Integration of copy number and transcriptomics provides risk stratification in prostate cancer: A discovery and validation cohort study.
Disease
View SamplesGoal: To examine the effects of human resistin during helminth infection. Methodology: To examine the function of human resistin (hResistin), we utilized transgenic mice expressing the human resistin gene along with its entire regulatory region (hRetnTg+). Following infection with the helminth Nippostrongylus brasiliensis, whole lung RNA was sequenced in hRetnTg+ mice, control hRetnTg- and naïve mice. Conclusion: In hRetnTg+ mice, many genes involved in inflammation and the immune system, specifically toll-like receptor signaling and chemokines, are significantly upregulated, suggesting that human resistin promotes TLR signaling and inflammation during helminth infection. Overall design: Examination of whole lung mRNA from Nippostrongylus brasiliensis-infected lungs at day 7 in mice expressing human resistin
Macrophage-derived human resistin is induced in multiple helminth infections and promotes inflammatory monocytes and increased parasite burden.
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View SamplesRNA-seq profiling was conducted on clinically-annotated human pancreatic adenocarcinoma cancer tissues Overall design: We measured the transcriptome in 51 clinically-annotated human pancreatic adenocarcinoma cancer tissues
RNA sequencing of pancreatic adenocarcinoma tumors yields novel expression patterns associated with long-term survival and reveals a role for ANGPTL4.
Age, Subject
View SamplesBackground: Germinal center B-cell (GCB) lymphomas are common in children and adults. The prognosis strongly depends on age. Subgroups of GCB-lymphomas are characterized by chromosomal translocations affecting immunoglobulin (IG) loci leading to oncogene deregulation.
Translocations activating IRF4 identify a subtype of germinal center-derived B-cell lymphoma affecting predominantly children and young adults.
Sex, Age
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