ArticleOncotarget2016
Genomic complexity and dynamics of clonal evolution in childhood acute myeloid leukemia studied with whole-exome sequencing.
Article in Oncotarget, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 37 citations in OpenAlex.
- A Novel Approach to Prognostic Factors and Risk Stratification in Pediatric AML: Case Report and Literature Review.International journal of molecular sciences · 2025Review
- Image-based drug screening combined with molecular profiling identifies signatures and drivers of therapy resistance in pediatric AML.Cell reports. Medicine · 2025Article
- The clinical utility and prognostic value of next-generation sequencing for measurable residual disease assessment in acute myeloid leukemia.Therapeutic advances in hematology · 2025Article
- Venetoclax: a new player in the treatment of children with high-risk myeloid malignancies?Blood advances · 2024Review
- Article
- Multi-omic analysis of longitudinal acute myeloid leukemia patient samples reveals potential prognostic markers linked to disease progression.Frontiers in genetics · 2024Article
- Article
- Cytogenetic and mutational analysis and outcome assessment of a cohort of 284 children with de novo acute myeloid leukemia reveal complex karyotype as an adverse risk factor for inferior survival.Molecular cytogenetics · 2021Article
- Exploiting Clonal Evolution to Improve the Diagnosis and Treatment Efficacy Prediction in Pediatric AML.Cancers · 2021Review
- Recurrent SETD2 mutation in NPM1-mutated acute myeloid leukemia.Biomarker research · 2020Article
- Insights on the Interplay between Cells Metabolism and Signaling: A Therapeutic Perspective in Pediatric Acute Leukemias.International journal of molecular sciences · 2020Review
- SET Domain Containing 2 Deficiency in Myelodysplastic Syndrome.Frontiers in genetics · 2020Article
- In Silico Genetics Revealing 5 Mutations inCancer informatics · 2019Article
- Using genomics to define pediatric blood cancers and inform practice.Hematology. American Society of Hematology. Education Program · 2018Review
- Article
- Sequential adaptive changes in a c-Myc-driven model of hepatocellular carcinoma.The Journal of biological chemistry · 2017Article
- Molecular and genetic alterations associated with therapy resistance and relapse of acute myeloid leukemia.Journal of hematology & oncology · 2017Review
Corrections and comments
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Authors and funding
14 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Despite significant improvement in treatment of childhood acute myeloid leukemia (AML), 30% of patients experience disease recurrence, which is still the major cause of treatment failure and death in these patients. To investigate molecular mechanisms underlying relapse, we performed whole-exome sequencing of diagnosis-relapse pairs and matched remission samples from 4 pediatric AML patients without recurrent cytogenetic alterations. Candidate driver mutations were selected for targeted deep sequencing at high coverage, suitable to detect small subclones (0.12%). BiCEBPα mutation was found to be stable and highly penetrant, representing a separate biological and clinical entity, unlike WT1 mutations, which were extremely unstable. Among the mutational patterns underlying relapse, we detected the acquisition of proliferative advantage by signaling activation (PTPN11 and FLT3-TKD mutations) and the increased resistance to apoptosis (hyperactivation of TYK2). We also found a previously undescribed feature of AML, consisting of a hypermutator phenotype caused by SETD2 inactivation. The consequent accumulation of new mutations promotes the adaptability of the leukemia, contributing to clonal selection. We report a novel ASXL3 mutation characterizing a very small subclone (<1%) present at diagnosis and undergoing expansion (60%) at relapse. Taken together, these findings provide molecular clues for designing optimal therapeutic strategies, in terms of target selection, adequate schedule design and reliable response-monitoring techniques.
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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.