ArticleHaematologica2021
Phase II-like murine trial identifies synergy between dexamethasone and dasatinib in T-cell acute lymphoblastic leukemia.
Article in Haematologica, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT06855810 (Chinese Children's Cancer Group T-cell Acute Lymphoblastic Leukemia -2025 Project), which is not on this map. Cited by 20 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Chinese Children's Cancer Group T-cell Acute Lymphoblastic Leukemia -2025 Project
Who cites it
20 citing papers in PubMed, 35 citations in OpenAlex.
- NFATc1 and NFATc2 regulate glucocorticoid resistance in pediatric T-cell acute lymphoblastic leukemia through modulation of cholesterol biosynthesis and the WNT/β-catenin pathway.Haematologica · 2026Article
- Review
- Advances in the application of patient-derived xenograft models in acute leukemia resistance.Cancer drug resistance (Alhambra, Calif.) · 2025Review
- Selection of dormant cells during treatment of T-lineage lymphoblastic leukemia and CREB as a therapeutic target.Haematologica · 2024Article
- Targeting hyperactive platelet-derived growth factor receptor-β signaling in T-cell acute lymphoblastic leukemia and lymphoma.Haematologica · 2024Article
- Hyperactive STAT5 hijacks T cell receptor signaling and drives immature T cell acute lymphoblastic leukemia.The Journal of clinical investigation · 2024Article
- Novel Biomarkers and Molecular Targets in ALL.Current hematologic malignancy reports · 2024Review
- Study Deciphering the Crucial Involvement of Notch Signaling Pathway in Human Cancers.Endocrine, metabolic & immune disorders drug targets · 2024Review
- Emerging Epigenetic and Posttranslational Mechanisms Controlling Resistance to Glucocorticoids in Acute Lymphoblastic Leukemia.HemaSphere · 2023Review
- Review
- Dasatinib regulates the proliferation and osteogenic differentiation of PDLSCs through Erk and EID3 signals.International journal of medical sciences · 2023Article
- Topical phenylbutyrate antagonizes NF-κB signaling and resolves corneal inflammation.iScience · 2022Article
- Oncogenic deubiquitination controls tyrosine kinase signaling and therapy response in acute lymphoblastic leukemia.Science advances · 2022Article
- Targeting Leukemia-Initiating Cells and Leukemic Niches: The Next Therapy Station for T-Cell Acute Lymphoblastic Leukemia?Cancers · 2022Review
- Therapeutic targeting of LCK tyrosine kinase and mTOR signaling in T-cell acute lymphoblastic leukemia.Blood · 2022Article
- Preclinical evaluation of proteolytic targeting of LCK as a therapeutic approach in T cell acute lymphoblastic leukemia.Science translational medicine · 2022Article
- Phosphoproteomic profiling of T cell acute lymphoblastic leukemia reveals targetable kinases and combination treatment strategies.Nature communications · 2022Article
- A human fetal liver-derived infant MLL-AF4 acute lymphoblastic leukemia model reveals a distinct fetal gene expression program.Nature communications · 2021Article
- The genomic landscape of teenage and young adult T-cell acute lymphoblastic leukemia.Cancer medicine · 2021Review
- T-cell Acute Lymphoblastic Leukemia: A Roadmap to Targeted Therapies.Blood cancer discovery · 2021Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
11 authors at 3 institutions in 2 countries.
Funding
Abstract
T-cell Acute Lymphoblastic Leukemia (T-ALL) is frequently characterized by glucocorticoid (GC) resistance, which is associated with inferior outcomes, thus highlighting the need for novel therapeutic approaches for GC resistant T-ALL. The pTCR/TCR signaling pathways play a critical role in cell fate decisions during physiological thymocyte development, with an interplay between TCR and glucocorticoid receptor (GR) signaling determining the T-lymphocyte selection process. We performed an shRNA screen in vitro and in vivo in T-ALL cell lines and patient derived xenograft (PDX) samples to identify vulnerabilities in the pTCR/TCR pathway and identified a critical role for the kinase LCK in cell proliferation. LCK knockdown or inhibition with dasatinib (DAS) caused cell cycle arrest. Combination of DAS with dexamethasone (DEX) resulted in significant drug synergy leading to cell death. The efficacy of this drug combination was underscored in a randomized phase II-like murine trial, recapitulating an early phase human clinical trial. T-ALL expansion in immunocompromised mice was significantly impaired using this drug combination, relative to mice receiving control vehicle or single drug treatment, highlighting the immediate clinical relevance of this drug combination for high risk T-ALL patients. Our results thus provide a strategy to improve the efficacy of current chemotherapy platforms and circumvent GC resistance.
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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 OpenQuestion graph.