ArticleBlood2014
Ras pathway mutations are prevalent in relapsed childhood acute lymphoblastic leukemia and confer sensitivity to MEK inhibition.
Article in Blood, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT00114348 (ALL-REZ BFM 2002), which is not on this map. Cited by 151 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.
ALL-REZ BFM 2002: Protocol for the Treatment of Children With Relapsed Acute Lymphoblastic Leukemia
Who cites it
151 citing papers in PubMed.
- Outcomes of patients with childhood B-cell precursor acute lymphoblastic leukaemia with late bone marrow relapses: long-term follow-up of the ALLR3 open-label randomised trial.The Lancet. Haematology · 2019Trial
- Clinical resistance to crenolanib in acute myeloid leukemia due to diverse molecular mechanisms.Nature communications · 2019Trial
- MAPK signaling cascades mediate distinct glucocorticoid resistance mechanisms in pediatric leukemia.Blood · 2015Trial
- Pathway incompatibility between NF-κB and RAS signaling constrains oncogenicity in B-cell leukemia.The Journal of biological chemistry · 2026Article
- Central nervous system involvement in acute lymphoblastic leukemia: pathogenesis and targeted therapy.Leukemia · 2026Review
- Combining menin and MEK inhibition to target poor prognosis KMT2A-rearranged RAS pathway-mutant acute myeloid leukemia.Blood advances · 2026Article
- TCF3::HLF-positive B-ALL: integrated clinical and molecular characterization of 34 cases from a single-center cohort.British journal of cancer · 2026Article
- Activity of Direct KRAS(G12C) Inhibitors in Preclinical Models of Pediatric Cancer.Molecular cancer therapeutics · 2026Article
- Transcriptomic validation of a 7,12 Dimethylbenz(a)anthracene (DMBA)-induced leukemia rat model: Parallels with human leukemogenesis.Animal models and experimental medicine · 2026Article
- The clinical characteristics and prognosis analysis of acute B-cell lymphoblastic leukemia with MEF2D fusions.Annals of hematology · 2026Article
- Review
- Review
- The Inositol-5-Phosphatase SHIP1: Expression, Regulation and Role in Acute Lymphoblastic Leukemia.International journal of molecular sciences · 2025Review
- Ex vivo drug responses and molecular profiles of 597 pediatric acute lymphoblastic leukemia patients.HemaSphere · 2025Article
- Dynamic evolution of TCF3-PBX1 leukemias at the single-cell level under chemotherapy pressure.HemaSphere · 2025Article
- Advances and Challenges in RAS Signaling Targeted Therapy in Leukemia.Molecular cancer therapeutics · 2025Review
- Transcriptome-based immune subtypes reveal the heterogeneity of tumor microenvironment in pediatric B-cell acute lymphocytic leukemia.Frontiers in oncology · 2025Article
- Preferential Genetic Pathways Lead to Relapses in Adult B-Cell Acute Lymphoblastic Leukemia.Cancers · 2024Article
- Article
- NK model simulation study of intelligent manufacturing transformation path selection in pharmaceutical manufacturing enterprises.Scientific reports · 2024Article
91 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
16 authors.
Funding
Abstract
For most children who relapse with acute lymphoblastic leukemia (ALL), the prognosis is poor, and there is a need for novel therapies to improve outcome. We screened samples from children with B-lineage ALL entered into the ALL-REZ BFM 2002 clinical trial (www.clinicaltrials.gov, #NCT00114348) for somatic mutations activating the Ras pathway (KRAS, NRAS, FLT3, and PTPN11) and showed mutation to be highly prevalent (76 from 206). Clinically, they were associated with high-risk features including early relapse, central nervous system (CNS) involvement, and specifically for NRAS/KRAS mutations, chemoresistance. KRAS mutations were associated with a reduced overall survival. Mutation screening of the matched diagnostic samples found many to be wild type (WT); however, by using more sensitive allelic-specific assays, low-level mutated subpopulations were found in many cases, suggesting that they survived up-front therapy and subsequently emerged at relapse. Preclinical evaluation of the mitogen-activated protein kinase kinase 1/2 inhibitor selumetinib (AZD6244, ARRY-142886) showed significant differential sensitivity in Ras pathway-mutated ALL compared with WT cells both in vitro and in an orthotopic xenograft model engrafted with primary ALL; in the latter, reduced RAS-mutated CNS leukemia. Given these data, clinical evaluation of selumetinib may be warranted for Ras pathway-mutated relapsed ALL.
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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.