Trial reportThe Journal of biological chemistry2013
CXCR4 chemokine receptor signaling induces apoptosis in acute myeloid leukemia cells via regulation of the Bcl-2 family members Bcl-XL, Noxa, and Bak.
Trial report in The Journal of biological chemistry, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 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
43 citing papers in PubMed, 1 synthesis or guideline pooled it, 90 citations in OpenAlex.
- Chemokines as Prognostic Factor in Colorectal Cancer Patients: A Systematic Review and Meta-Analysis.International journal of molecular sciences · 2024Pooled it
- Molecular dissection of valproic acid effects in acute myeloid leukemia identifies predictive networks.Epigenetics · 2016Trial
- Mcl-1 dependence predicts response to vorinostat and gemtuzumab ozogamicin in acute myeloid leukemia.Leukemia research · 2014Trial
- Diagnostic and Prognostic Significance of Chemokines in Head and Neck Cancers: A Systematic Review and Meta-Analysis.Cancers · 2026Review
- BCL-2 and BCL-xL in Cancer: Regulation, Function, and Therapeutic Targeting.International journal of molecular sciences · 2026Review
- Identification of Immune-Related Genes in Predicting the Progression of Colitis-Associated Colorectal Cancer: An Integrated Bioinformatics and Experimental Validation Study.Journal of inflammation research · 2026Article
- TP53-Mutated Acute Myeloid Leukemia: Unanswered Questions.Hematological oncology · 2025Review
- Establishment of prognostic signature based on neutrophil extracellular traps-related genes in acute myeloid leukemia: a bioinformatics analysis.Frontiers in immunology · 2025Article
- CXCR4 as a therapeutic target in acute myeloid leukemia.Leukemia · 2024Review
- Novel Anti-Enterovirus A71 Compounds Discovered by Repositioning Antivirals from the Open-Source MMV Pandemic Response Box.Pharmaceuticals (Basel, Switzerland) · 2024Article
- A hypoxia-related genes prognostic risk model, and mechanisms of hypoxia contributing to poor prognosis through immune microenvironment and drug resistance in acute myeloid leukemia.Frontiers in pharmacology · 2024Article
- CRISPR screens identify novel regulators of cFLIP dependency and ligand-independent, TRAIL-R1-mediated cell death.Cell death and differentiation · 2023Article
- Review
- Construction of an acute myeloid leukemia prognostic model based on m6A-related efferocytosis-related genes.Frontiers in immunology · 2023Article
- ScRNA-seq revealed targeting regulator of G protein signaling 1 to mediate regulatory T cells in Hepatocellular carcinoma.Cancer biomarkers : section A of Disease markers · 2023Article
- Article
- ABAT gene expression associated with the sensitivity of hypomethylating agents in myelodysplastic syndrome through CXCR4/mTOR signaling.Cell death discovery · 2022Article
- Functional Tumor Targeting Nano-Systems for Reprogramming Circulating Tumor Cells with In Situ Evaluation on Therapeutic Efficiency at the Single-Cell Level.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2022Article
- Effect of erythropoietin administration on expression of mRNA brain-derived Neutrophic factor, levels of stromal cell-derived Factor-1, and neuron specific enolase in brain injury modelAnnals of medicine and surgery (2012) · 2021Article
- A hypoxia risk signature for the tumor immune microenvironment evaluation and prognosis prediction in acute myeloid leukemia.Scientific reports · 2021Article
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 1 country.
Funding
Abstract
The CXCR4 chemokine receptor promotes survival of many different cell types. Here, we describe a previously unsuspected role for CXCR4 as a potent inducer of apoptosis in acute myeloid leukemia (AML) cell lines and a subset of clinical AML samples. We show that SDF-1, the sole ligand for CXCR4, induces the expected migration and ERK activation in the KG1a AML cell line transiently overexpressing CXCR4, but ERK activation did not lead to survival. Instead, SDF-1 treatment led via a CXCR4-dependent mechanism to apoptosis, as evidenced by increased annexin V staining, condensation of chromatin, and cleavage of both procaspase-3 and PARP. This SDF-1-induced death pathway was partially inhibited by hypoxia, which is often found in the bone marrow of AML patients. SDF-1-induced apoptosis was inhibited by dominant negative procaspase-9 but not by inhibition of caspase-8 activation, implicating the intrinsic apoptotic pathway. Further analysis showed that this pathway was activated by multiple mechanisms, including up-regulation of Bak at the level of mRNA and protein, stabilization of the Bak activator Noxa, and down-regulation of antiapoptotic Bcl-XL. Furthermore, adjusting expression levels of Bak, Bcl-XL, or Noxa individually altered the level of apoptosis in AML cells, suggesting that the combined modulation of these family members by SDF-1 coordinates their interplay to produce apoptosis. Thus, rather than mediating survival, SDF-1 may be a means to induce apoptosis of CXCR4-expressing AML cells directly in the SDF-1-rich bone marrow microenvironment if the survival cues of the bone marrow are disrupted.
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What OpenQuestion holds
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.