ArticleOncotarget2016
Anti-apoptotic ARC protein confers chemoresistance by controlling leukemia-microenvironment interactions through a NFκB/IL1β signaling network.
Article in Oncotarget, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
28 citing papers in PubMed, 38 citations in OpenAlex.
- Role of apoptosis repressor with caspase recruitment domain in human health and chronic diseases.Annals of medicine · 2024Review
- Differential inflammatory conditioning of the bone marrow by acute myeloid leukemia and its impact on progression.Blood advances · 2024Article
- Mesenchymal Stem Cells in Myelodysplastic Syndromes and Leukaemia.Biomedicines · 2024Review
- Leukemic Stem Cells and Hematological Malignancies.International journal of molecular sciences · 2024Review
- Biology and Therapeutic Properties of Mesenchymal Stem Cells in Leukemia.International journal of molecular sciences · 2024Review
- A double-edged sword: role of apoptosis repressor with caspase recruitment domain (ARC) in tumorigenesis and ischaemia/reperfusion (I/R) injury.Apoptosis : an international journal on programmed cell death · 2023Review
- Mesenchymal stroma/stem cells: Haematologists' friend or foe?British journal of haematology · 2022Review
- Review
- Aberrantly low STAT3 and STAT5 responses are associated with poor outcome and an inflammatory gene expression signature in pediatric acute myeloid leukemia.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2021Article
- Expression of apoptosis repressor with caspase recruitment domain (ARC) in familial adenomatous polyposis (FAP) adenomas and its correlation with DNA mismatch repair proteins, p53, Bcl-2, COX-2 and beta-catenin.Cell communication and signaling : CCS · 2021Article
- Leukemic Stem Cells: From Leukemic Niche Biology to Treatment Opportunities.Frontiers in immunology · 2021Review
- The Bone Marrow Microenvironment Mechanisms in Acute Myeloid Leukemia.Frontiers in cell and developmental biology · 2021Review
- Expression profiling of some Acute Myeloid Leukemia - associated markers to assess their diagnostic / prognostic potential.Genetics and molecular biology · 2021Article
- Bone Marrow Mesenchymal Stem Cells Support Acute Myeloid Leukemia Bioenergetics and Enhance Antioxidant Defense and Escape from Chemotherapy.Cell metabolism · 2020Article
- Location First: Targeting Acute Myeloid Leukemia Within Its Niche.Journal of clinical medicine · 2020Review
- Mesenchymal Stromal Cells as a Cellular Target in Myeloid Malignancy: Chances and Challenges in the Genome Editing of Stromal Alterations.Frontiers in genome editing · 2020Review
- Role of CC Chemokines Subfamily in the Platinum Drugs Resistance Promotion in Cancer.Frontiers in immunology · 2020Review
- Role of apoptosis repressor with caspase recruitment domain (ARC) in cancer.Oncology letters · 2019Review
- A Role for Lipid Mediators in Acute Myeloid Leukemia.International journal of molecular sciences · 2019Review
- An ARC-Regulated IL1β/Cox-2/PGE2/β-Catenin/ARC Circuit Controls Leukemia-Microenvironment Interactions and Confers Drug Resistance in AML.Cancer research · 2019Article
Corrections and comments
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Authors and funding
12 authors at 2 institutions in 2 countries.
Funding
Abstract
To better understand how the apoptosis repressor with caspase recruitment domain (ARC) protein confers drug resistance in acute myeloid leukemia (AML), we investigated the role of ARC in regulating leukemia-mesenchymal stromal cell (MSC) interactions. In addition to the previously reported effect on AML apoptosis, we have demonstrated that ARC enhances migration and adhesion of leukemia cells to MSCs both in vitro and in a novel human extramedullary bone/bone marrow mouse model. Mechanistic studies revealed that ARC induces IL1β expression in AML cells and increases CCL2, CCL4, and CXCL12 expression in MSCs, both through ARC-mediated activation of NFκB. Expression of these chemokines in MSCs increased by AML cells in an ARC/IL1β-dependent manner; likewise, IL1β expression was elevated when leukemia cells were co-cultured with MSCs. Further, cells from AML patients expressed the receptors for and migrated toward CCL2, CCL4, and CXCL12. Inhibition of IL1β suppressed AML cell migration and sensitized the cells co-cultured with MSCs to chemotherapy. Our results suggest the existence of a complex ARC-regulated circuit that maintains intimate connection of AML with the tumor microenvironment through NFκB/IL1β-regulated chemokine receptor/ligand axes and reciprocal crosstalk resulting in cytoprotection. The data implicate ARC as a promising drug target to potentially sensitize AML cells to chemotherapy.
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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.