ArticleCancers2020
CXCR4 Inhibition Enhances Efficacy of FLT3 Inhibitors in FLT3-Mutated AML Augmented by Suppressed TGF-b Signaling.
Article in Cancers, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 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.
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Who cites it
11 citing papers in PubMed, 14 citations in OpenAlex.
- Multi-omics integration of molecular genetics, cytogenetics and immunophenotyping: a novel prognostic model for immune landscape characterization and outcome prediction in Chinese patients with acute myeloid leukemia.Frontiers in immunology · 2026Article
- Counter-Therapeutic Strategies for Resistance of FLT3 Inhibitors in Acute Myeloid Leukemia.Cells · 2025Review
- Marine derived macrolide bryostatin 4 inhibits the TGF-β signaling pathway against acute erythroleukemia.Cellular oncology (Dordrecht, Netherlands) · 2024Article
- Age-related dysregulation of intestinal epithelium fucosylation is linked to an increased risk of colon cancer.JCI insight · 2024Article
- Targeting FLT3 Mutation in Acute Myeloid Leukemia: Current Strategies and Future Directions.Cancers · 2023Review
- Article
- The interplay of FLT3 and CXCR4 in acute myeloid leukemia: an ongoing debate.Frontiers in oncology · 2023Review
- Utilization of macrocyclic peptides to target protein-protein interactions in cancer.Frontiers in oncology · 2022Review
- Role of CXCR4 in the progression and therapy of acute leukaemia.Cell proliferation · 2021Review
- Dysregulation of miR-138-5p/RPS6KA1-AP2M1 Is Associated With Poor Prognosis in AML.Frontiers in cell and developmental biology · 2021Article
- Article
Corrections and comments
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Authors and funding
11 authors at 3 institutions in 2 countries.
Funding
Abstract
Given the proven importance of the CXCL12/CXCR4 axis in the stroma-acute myeloid leukemia (AML) interactions and the rapid emergence of resistance to FLT3 inhibitors, we investigated the efficacy and safety of a novel CXCR4 inhibitor, LY2510924, in combination with FLT3 inhibitors in preclinical models of AML with FLT3-ITD mutations (FLT3-ITD-AML). Quizartinib, a potent FLT3 inhibitor, induced apoptosis in FLT3-ITD-AML, while LY2510924 blocked surface CXCR4 without inducing apoptosis. LY2510924 significantly reversed stroma-mediated resistance against quizartinib mainly through the MAPK pathway. In mice with established FLT3-ITD-AML, LY2510924 induced durable mobilization and differentiation of leukemia cells, resulting in enhanced anti-leukemia effects when combined with quizartinib, whereas transient effects were seen on non-leukemic blood cells in immune-competent mice. Sequencing of the transcriptome of the leukemic cells surviving in vivo treatment with quizartinib and LY2510924 revealed that genes related to TGF-b signaling may confer resistance against the drug combination. In co-culture experiments of FLT3-ITD-AML and stromal cells, both silencing of TGF-b in stromal cells or TGF-b-receptor kinase inhibitor enhanced apoptosis by combined treatment. Disruption of the CXCL12/CXCR4 axis in FLT3-ITD-AML by LY2510924 and its negligible effects on normal immunocytes could safely enhance the potency of quizartinib, which may be further improved by blockade of TGF-b signaling.
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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.