Trial reportHaematologica2015
Pediatric T-cell lymphoblastic leukemia evolves into relapse by clonal selection, acquisition of mutations and promoter hypomethylation.
Trial report in Haematologica, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 53 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
53 citing papers in PubMed, 81 citations in OpenAlex.
- MAP3K7 is recurrently deleted in pediatric T-lymphoblastic leukemia and affects cell proliferation independently of NF-κB.BMC cancer · 2018Trial
- Comprehensive Epigenome-Wide Profiling Reveals Distinctive DNA Methylation Signatures and Potential Prognostic Biomarkers in Mexican Pediatric B-ALL.International journal of molecular sciences · 2025Article
- Role of stem-like cells in chemotherapy resistance and relapse in pediatric T-cell acute lymphoblastic leukemia.Nature communications · 2025Article
- Genetic evolution and relapse-associated mutations in adult T-cell acute lymphoblastic leukemia patients treated in PETHEMA trials.HemaSphere · 2025Article
- Review
- Subclonal TP53 and KRAS variants combined with poor treatment response identify ultrahigh-risk pediatric patients with T-ALL.Blood advances · 2025Article
- Acute lymphoblastic leukaemia.Nature reviews. Disease primers · 2024Review
- Pediatric T-cell acute lymphoblastic leukemia blast signature and MRD associated immune environment changes defined by single cell transcriptomics analysis.Scientific reports · 2023Article
- Comprehensive analysis of mutational signatures reveals distinct patterns and molecular processes across 27 pediatric cancers.Nature cancer · 2023Article
- The NT5DC family: expression profile and prognostic value in pancreatic adenocarcinoma.Journal of Cancer · 2023Article
- Pediatric T-ALL type-1 and type-2 relapses develop along distinct pathways of clonal evolution.Leukemia · 2022Article
- Controversial Flow Cytometry Monitoring of a Relapse Case of Pediatric T Cell Acute Lymphoblastic Leukemia: A Case Report.Frontiers in medicine · 2022Article
- The Genomic Landscape of a Restricted ALL Cohort from Patients Residing on the U.S./Mexico Border.International journal of environmental research and public health · 2021Article
- The genomic landscape of teenage and young adult T-cell acute lymphoblastic leukemia.Cancer medicine · 2021Review
- The New Therapeutic Strategies in Pediatric T-Cell Acute Lymphoblastic Leukemia.International journal of molecular sciences · 2021Review
- Comprehensive Overview of Gene Rearrangements in Childhood T-Cell Acute Lymphoblastic Leukaemia.International journal of molecular sciences · 2021Review
- The evolution of relapse of adult T cell acute lymphoblastic leukemia.Genome biology · 2020Article
- Mutational and functional genetics mapping of chemotherapy resistance mechanisms in relapsed acute lymphoblastic leukemia.Nature cancer · 2020Article
- Determination of NUDT15 variants by targeted sequencing can identify compound heterozygosity in pediatric acute lymphoblastic leukemia patients.Scientific reports · 2020Article
- Loss of glucocorticoid receptor expression mediates in vivo dexamethasone resistance in T-cell acute lymphoblastic leukemia.Leukemia · 2020Article
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Authors and funding
23 authors at 9 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Relapsed precursor T-cell acute lymphoblastic leukemia is characterized by resistance against chemotherapy and is frequently fatal. We aimed at understanding the molecular mechanisms resulting in relapse of T-cell acute lymphoblastic leukemia and analyzed 13 patients at first diagnosis, remission and relapse by whole exome sequencing, targeted ultra-deep sequencing, multiplex ligation dependent probe amplification and DNA methylation array. Compared to primary T-cell acute lymphoblastic leukemia, in relapse the number of single nucleotide variants and small insertions and deletions approximately doubled from 11.5 to 26. Targeted ultra-deep sequencing sensitively detected subclones that were selected for in relapse. The mutational pattern defined two types of relapses. While both are characterized by selection of subclones and acquisition of novel mutations, 'type 1' relapse derives from the primary leukemia whereas 'type 2' relapse originates from a common pre-leukemic ancestor. Relapse-specific changes included activation of the nucleotidase NT5C2 resulting in resistance to chemotherapy and mutations of epigenetic modulators, exemplified by SUZ12, WHSC1 and SMARCA4. While mutations present in primary leukemia and in relapse were enriched for known drivers of leukemia, relapse-specific changes revealed an association with general cancer-promoting mechanisms. This study thus identifies mechanisms that drive progression of pediatric T-cell acute lymphoblastic leukemia to relapse and may explain the characteristic treatment resistance of this condition.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.