ArticleBlood2009
Targeting the leukemia microenvironment by CXCR4 inhibition overcomes resistance to kinase inhibitors and chemotherapy in AML.
Article in Blood, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 282 papers, 1 of them a synthesis that pooled it.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
282 citing papers in PubMed, 1 synthesis or guideline pooled it, 509 citations in OpenAlex.
- A Direct Comparison, and Prioritisation, of the Immunotherapeutic Targets Expressed by Adult and Paediatric Acute Myeloid Leukaemia Cells: A Systematic Review and Meta-Analysis.International journal of molecular sciences · 2023Pooled it
- Trial
- Results from a phase I/II trial of cusatuzumab combined with azacitidine in patients with newly diagnosed acute myeloid leukemia who are ineligible for intensive chemotherapy.Haematologica · 2023Trial
- Proteomic Profiling of Signaling Networks Modulated by G-CSF/Plerixafor/Busulfan-Fludarabine Conditioning in Acute Myeloid Leukemia Patients in Remission or with Active Disease prior to Allogeneic Stem Cell Transplantation.Acta haematologica · 2019Trial
- Combination of the low anticoagulant heparin CX-01 with chemotherapy for the treatment of acute myeloid leukemia.Blood advances · 2018Trial
- Randomized phase II trial of cytosine arabinoside with and without the CHK1 inhibitor MK-8776 in relapsed and refractory acute myeloid leukemia.Leukemia research · 2017Trial
- A phase 1/2 study of chemosensitization with plerixafor plus G-CSF in relapsed or refractory acute myeloid leukemia.Blood cancer journal · 2017Trial
- LPCAT3 is essential for leukemia progression and represents a therapeutic vulnerability in AML.Blood science (Baltimore, Md.) · 2026Article
- Longitudinal localization of leukaemic stem cells between the metaphysis and central marrow governs their behaviour.Nature cell biology · 2026Article
- Metabolic and epigenetic interplay in HSPC specification: A balance between extrinsic and intrinsic cues.iScience · 2026Review
- Overcoming therapeutic challenges in acute myeloid leukemia: active targeting strategies by nano-drug delivery systems.Journal of translational medicine · 2026Review
- Dynamic heterogeneity towards drug resistance in AML cells is primarily driven by epigenomic mechanism unveiled by multi-omics analysis.Journal of advanced research · 2026Article
- Exploring the Bone Marrow Microenvironment as a Therapeutic Barrier and Targetable Source of Crosstalk in Acute Myeloid Leukemia.Blood and lymphatic cancer : targets and therapy · 2026Review
- Functional-genomic prioritization identifiesFrontiers in pharmacology · 2026Article
- CXCL12 chemokine dimer signaling modulates acute myelogenous leukemia cell migration through altered receptor internalization.Scientific reports · 2025Article
- Dual targeting of CXC chemokine receptor 4 and multidrug resistance protein 1 by ZIN056 effectively combat daunorubicin resistance in acute myeloid leukemia cells.Medical oncology (Northwood, London, England) · 2025Article
- Dysregulation of MicroRNA-181a-5p Targets TNFAIP3 to Promote MIF-CXCR4 Signaling and Immune Inflammatory Remodeling in Chronic Myeloid Leukemia.F1000Research · 2025Article
- Pioneering biomimetic biomaterial for leukemia therapy enhancement: a review.Frontiers in bioengineering and biotechnology · 2025Review
- Bioinformatics-guided construction of a tumor microenvironment-derived prognostic model in acute myeloid leukemia.PloS one · 2025Article
- CXCR4 as a therapeutic target in acute myeloid leukemia.Leukemia · 2024Review
222 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
13 authors at 4 institutions in 1 country.
Funding
Abstract
SDF-1alpha/CXCR4 signaling plays a key role in leukemia/bone marrow microenvironment interactions. We previously reported that bone marrow-derived stromal cells inhibit chemotherapy-induced apoptosis in acute myeloid leukemia (AML). Here we demonstrate that the CXCR4 inhibitor AMD3465 antagonized stromal-derived factor 1alpha (SDF-1alpha)-induced and stroma-induced chemotaxis and inhibited SDF-1alpha-induced activation of prosurvival signaling pathways in leukemic cells. Further, CXCR4 inhibition partially abrogated the protective effects of stromal cells on chemotherapy-induced apoptosis in AML cells. Fetal liver tyrosine kinase-3 (FLT3) gene mutations activate CXCR4 signaling, and coculture with stromal cells significantly diminished antileukemia effects of FLT3 inhibitors in cells with mutated FLT3. Notably, CXCR4 inhibition increased the sensitivity of FLT3-mutated leukemic cells to the apoptogenic effects of the FLT3 inhibitor sorafenib. In vivo studies demonstrated that AMD3465, alone or in combination with granulocyte colony-stimulating factor, induced mobilization of AML cells and progenitor cells into circulation and enhanced antileukemic effects of chemotherapy and sorafenib, resulting in markedly reduced leukemia burden and prolonged survival of the animals. These findings indicate that SDF-1alpha/CXCR4 interactions contribute to the resistance of leukemic cells to signal transduction inhibitor- and chemotherapy-induced apoptosis in systems mimicking the physiologic microenvironment. Disruption of these interactions with CXCR4 inhibitors represents a novel strategy of sensitizing leukemic cells by targeting their protective bone marrow microenvironment.
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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.