This SuperSeries is composed of the SubSeries listed below.
Biologic pathways associated with relapse in childhood acute lymphoblastic leukemia: a Children's Oncology Group study.
No sample metadata fields
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.
No sample metadata fields
View SamplesWe identified germline single nucleotide polymorphisms (SNPs) associated with childhood acute lymphoblastic leukemia (ALL) and its subtypes. Using the Affymetrix 500K Mapping array and publicly available genotypes, we identified 18 SNPs whose allele frequency differed (P<1x10-5) between a pediatric ALL population (n=317) and non-ALL controls (n=17,958). Six of these SNPs differed (P0.05) in allele frequency among four ALL subtypes. Two SNPs in ARID5B not only differed between ALL and non-ALL groups (rs10821936, P=1.4x10-15, odds ratio[OR]=1.91; rs10994982, P=5.7x10-9, OR=1.62) but also distinguished B-hyperdiploid ALL from other subtypes (rs10821936, P=1.62 x10-5, OR=2.17; rs10994982, P=0.003, OR 1.72). These ARID5B SNPs also distinguished B-hyperdiploid ALL from other subtypes in an independent validation cohort (n=124 children with ALL) (P=0.003 and P=0.0008, OR 2.45 and 2.86, respectively) and were associated with methotrexate accumulation and gene expression pattern in leukemic lymphoblasts. We conclude that germline genomic variations affect susceptibility to and characteristics of specific ALL subtypes.
Germline genomic variants associated with childhood acute lymphoblastic leukemia.
Specimen part, Disease
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 SamplesWe profiled the transcriptome of matched diagnosis and relapse samples from 10 pediatric B precursor Acute Lymphoblastic Leukemia (ALL) patients using massively parallel sequencing (RNA-Seq) technology to identify novel mutations specific at disease recurrence.
Relapse-specific mutations in NT5C2 in childhood acute lymphoblastic leukemia.
No sample metadata fields
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 SamplesPrimary xenografts were made from a variety of different high-risk childhood BCP-ALL leukemia samples.
Evaluation of the in vitro and in vivo efficacy of the JAK inhibitor AZD1480 against JAK-mutated acute lymphoblastic leukemia.
Specimen part
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.
No sample metadata fields
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
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