ArticleClinical cancer research : an official journal of the American Association for Cancer Research2020
Constitutive Activation of RAS/MAPK Pathway Cooperates with Trisomy 21 and Is Therapeutically Exploitable in Down Syndrome B-cell Leukemia.
Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 23 citations in OpenAlex.
- Spatially resolved multiomics of human meningeal development reveal lineage and disease dynamics.Nature cell biology · 2026Article
- Non-Invasive Prenatal Screening for Down Syndrome: A Review of Mass-Spectrometry-Based Approaches.Life (Basel, Switzerland) · 2025Review
- Secondary lesions and sensitivity to signaling inhibitors in iAMP21 acute lymphoblastic leukemia.HemaSphere · 2025Article
- DYRK1A in blood and immune function: implications in leukemia, inflammatory disorders, infection and Down syndrome.Frontiers in cell and developmental biology · 2025Review
- Efficacy of DYRK1A inhibitors in novel models of Down syndrome acute lymphoblastic leukemia.Haematologica · 2024Article
- Insights into the Clinical, Biological and Therapeutic Impact of Copy Number Alteration in Cancer.International journal of molecular sciences · 2024Review
- Down syndrome-associated leukaemias: current evidence and challenges.Therapeutic advances in hematology · 2024Review
- Down syndrome and leukemia: from basic mechanisms to clinical advances.Haematologica · 2023Review
- A biobank of pediatric patient-derived-xenograft models in cancer precision medicine trial MAPPYACTS for relapsed and refractory tumors.Communications biology · 2023Article
- Gain of chromosome 21 increases the propensity forFrontiers in oncology · 2023Article
- Detection of Embryonic Trisomy 21 in the First Trimester Using Maternal Plasma Cell-Free RNA.Diagnostics (Basel, Switzerland) · 2022Article
- Drug-Targeted Genomes: Mutability of Ion Channels and GPCRs.Biomedicines · 2022Article
- Article
- Building the Future Therapies for Down Syndrome: The Third International Conference of the T21 Research Society.Molecular syndromology · 2021Article
- DYRK1A regulates B cell acute lymphoblastic leukemia through phosphorylation of FOXO1 and STAT3.The Journal of clinical investigation · 2021Article
- Characterization of ROS Metabolic Equilibrium Reclassifies Pan-Cancer Samples and Guides Pathway Targeting Therapy.Frontiers in oncology · 2020Article
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Authors and funding
30 authors at 10 institutions in 5 countries.
Funding
Abstract
purposeChildren with Down syndrome (constitutive trisomy 21) that develop acute lymphoblastic leukemia (DS-ALL) have a 3-fold increased likelihood of treatment-related mortality coupled with a higher cumulative incidence of relapse, compared with other children with B-cell acute lymphoblastic leukemia (B-ALL). This highlights the lack of suitable treatment for Down syndrome children with B-ALL. EXPERIMENTAL
designTo facilitate the translation of new therapeutic agents into clinical trials, we built the first preclinical cohort of patient-derived xenograft (PDX) models of DS-ALL, comprehensively characterized at the genetic and transcriptomic levels, and have proven its suitability for preclinical studies by assessing the efficacy of drug combination between the MEK inhibitor trametinib and conventional chemotherapy agents.
resultsWhole-exome and RNA-sequencing experiments revealed a high incidence of somatic alterations leading to RAS/MAPK pathway activation in our cohort of DS-ALL, as well as in other pediatric B-ALL presenting somatic gain of the chromosome 21 (B-ALL+21). In murine and human B-cell precursors, activated KRAS
conclusionsAltogether, using novel and suitable PDX models, this study indicates that RAS/MAPK pathway inhibition represents a promising strategy to improve the outcome of Down syndrome children with B-cell precursor leukemia.
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Registered trials
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 Socratic graph.