ArticleLeukemia2018
RAS pathway mutations as a predictive biomarker for treatment adaptation in pediatric B-cell precursor acute lymphoblastic leukemia.
Article in Leukemia, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 67 papers.
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Who cites it
67 citing papers in PubMed, 111 citations in OpenAlex.
- Integrated analysis of relapsed B-cell precursor Acute Lymphoblastic Leukemia identifies subtype-specific cytokine and metabolic signatures.Scientific reports · 2019Trial
- Trial
- Pathway incompatibility between NF-κB and RAS signaling constrains oncogenicity in B-cell leukemia.The Journal of biological chemistry · 2026Article
- Genomic profiling of Mexican patients with B-cell precursor acute lymphoblastic leukemia reveals clinically significant somatic and potential germline variants.The journal of pathology. Clinical research · 2026Article
- The clinical relevance of RAS pathway gene mutations in childhood B-cell acute lymphoblastic leukemia.Annals of hematology · 2026Article
- Integrated Genomic Profiling of Pediatric Acute Lymphoblastic Leukemia: Genomic Landscape, Risk Stratification and Association of RAS Pathway Mutations with Early Treatment Response.International journal of molecular sciences · 2026Article
- Multi-Omics Applications in Adult Acute Lymphoblastic Leukemia: From Biological Mechanisms to Precision Therapies.International journal of molecular sciences · 2026Review
- Review
- Article
- Low expression of CADPS predicts poor prognosis in pediatric acute lymphoblastic leukemia without fusion genes.Biomolecules & biomedicine · 2025Article
- Network pharmacology and AI in cancer research uncovering biomarkers and therapeutic targets for RALGDS mutations.Scientific reports · 2025Article
- Discovery of Cis-Regulatory Mechanisms via Non-Coding Mutations in Acute Lymphoblastic Leukemia.Genes, chromosomes & cancer · 2025Article
- Somatic mtDNA mutation burden shapes metabolic plasticity in leukemogenesis.Science advances · 2025Article
- Advances and Challenges in RAS Signaling Targeted Therapy in Leukemia.Molecular cancer therapeutics · 2025Review
- Secondary lesions and sensitivity to signaling inhibitors in iAMP21 acute lymphoblastic leukemia.HemaSphere · 2025Article
- Patient-derived rhabdomyosarcoma cells recapitulate the genetic and transcriptomic landscapes of primary tumors.iScience · 2024Article
- DistinctInternational journal of molecular sciences · 2024Article
- Characterisation of FLT3 alterations in childhood acute lymphoblastic leukaemia.British journal of cancer · 2024Article
- Comprehensive genomic characterization of hematologic malignancies at a pediatric tertiary care center.Frontiers in oncology · 2024Article
- Comprehensive characterization of patient-derived xenograft models of pediatric leukemia.iScience · 2023Article
7 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
17 authors at 5 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
RAS pathway mutations have been linked to relapse and chemotherapy resistance in pediatric B-cell precursor acute lymphoblastic leukemia (BCP-ALL). However, comprehensive data on the frequency and prognostic value of subclonal mutations in well-defined subgroups using highly sensitive and quantitative methods are lacking. Targeted deep sequencing of 13 RAS pathway genes was performed in 461 pediatric BCP-ALL cases at initial diagnosis and in 19 diagnosis-relapse pairs. Mutations were present in 44.2% of patients, with 24.1% carrying a clonal mutation. Mutation frequencies were highest in high hyperdiploid, infant t(4;11)-rearranged, BCR-ABL1-like and B-other cases (50-70%), whereas mutations were less frequent in ETV6-RUNX1-rearranged, and rare in TCF3-PBX1- and BCR-ABL1-rearranged cases (27-4%). RAS pathway-mutated cells were more resistant to prednisolone and vincristine ex vivo. Clonal, but not subclonal, mutations were linked to unfavorable outcome in standard- and high-risk-treated patients. At relapse, most RAS pathway mutations were clonal (9 of 10). RAS mutant cells were sensitive to the MEK inhibitor trametinib ex vivo, and trametinib sensitized resistant cells to prednisolone. We conclude that RAS pathway mutations are frequent, and that clonal, but not subclonal, mutations are associated with unfavorable risk parameters in newly diagnosed pediatric BCP-ALL. These mutations may designate patients eligible for MEK inhibitor treatment.
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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.