T-cell acute lymphoblastic leukemia (T-ALL) and T-cell lymphoblastic lymphoma (T-LL) and are often thought to represent a spectrum of a single disease. The malignant cells in T-ALL and T-LL are morphologically indistinguishable, and they share the expression of common cell surface antigens and cytogenetic characteristics. However, despite these similarities, differences in the predominant sites of disease in T-ALL and T-LL are observed. To determine if underlying biological distinctions may potentially contribute to some of these differences, we analyzed the global gene expression profiles of malignant T-cell precursors in ten T-ALL and nine T-LL using DNA arrays. Ten additional B-precursor ALL bone marrow samples, were used in a separate analysis.
Gene expression profiling reveals intrinsic differences between T-cell acute lymphoblastic leukemia and T-cell lymphoblastic lymphoma.
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Biologic pathways associated with relapse in childhood acute lymphoblastic leukemia: a Children's Oncology Group study.
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View Samples35 paired samples from initial diagnosis and first marrow relapse. Genes and pathways differentiating diagnosis and relapse were identified. Potential therapeutic targets were also identified.
Biologic pathways associated with relapse in childhood acute lymphoblastic leukemia: a Children's Oncology Group study.
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View SamplesThis SuperSeries is composed of the SubSeries listed below.
Integrated genomic analysis of relapsed childhood acute lymphoblastic leukemia reveals therapeutic strategies.
Specimen part, Disease
View SamplesThere is a distinct signature of differentially expressed probes from diagnosis to relapse
Integrated genomic analysis of relapsed childhood acute lymphoblastic leukemia reveals therapeutic strategies.
Specimen part, Disease
View SamplesGene expression profiling (GEP) can reveal characteristic signatures associated with distinct biologic subtypes of acute lymphoblastic leukemia (ALL).
Genomic profiling in Down syndrome acute lymphoblastic leukemia identifies histone gene deletions associated with altered methylation profiles.
Specimen part, Disease
View SamplesPatients with Down syndrome (DS) and acute lymphoblastic leukemia (ALL) have distinct clinical and biological features. Whereas most DS-ALL cases lack the sentinel cytogenetic lesions that guide risk assignment in childhood ALL, JAK2 mutations and CRLF2 overexpression are highly enriched. To further characterize the unique biology of DS-ALL, we performed genome-wide profiling of 58 DS-ALL and 35 non-Down syndrome (NDS) ALL cases by DNA copy number, loss of heterozygosity, gene expression, and methylation analyses. We report novel deletions within the 6p22 histone gene cluster as significantly more frequent in DS-ALL, occurring in 12 DS (24%) and only a single NDS case (3%) (Fishers exact p = 0.013). Homozygous deletions yielded significantly lower histone expression levels, and were associated with higher methylation levels, distinct spatial localization of methylated promoters, and enrichment of highly methylated genes for specific pathways and transcription factor binding motifs. Gene expression profiling identified CRLF2 overexpression in nearly half DS-ALL cases, and supervised analysis identified an associated 39-gene signature. However, no expression signature was identified for DS-ALL overall, nor for histone status, suggesting that DS-ALL constitutes several, heterogeneous molecular entities. Characterization of pathways associated with histone deletions and high CRLF2 expression may identify opportunities for novel targeted interventions.
Genomic profiling in Down syndrome acute lymphoblastic leukemia identifies histone gene deletions associated with altered methylation profiles.
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View SamplesGene Expression Classifiers for Minimal Residual Disease and Relapse Free Survival Improve Outcome Prediction and Risk Classification in Children with High Risk Acute Lymphoblastic Leukemia: A Children's Oncology Group Study
Gene expression classifiers for relapse-free survival and minimal residual disease improve risk classification and outcome prediction in pediatric B-precursor acute lymphoblastic leukemia.
Specimen part, Disease, Disease stage
View SamplesPAPER 1:"Identification of novel subgroups of high-risk pediatric precursor B acute lymphoblastic leukemia (B-ALL) by unsupervised microarray analysis: clinical correlates and therapeutic implications. A Children's Oncology Group (COG) study."
Gene expression classifiers for relapse-free survival and minimal residual disease improve risk classification and outcome prediction in pediatric B-precursor acute lymphoblastic leukemia.
Sex, Specimen part, Race
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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