Trial reportBritish journal of haematology2015
Stromal CYR61 Confers Resistance to Mitoxantrone via Spleen Tyrosine Kinase Activation in Human Acute Myeloid Leukaemia.
Trial report in British journal of haematology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
26 citing papers in PubMed, 35 citations in OpenAlex.
- Effect of vitamin D status on a disintegrin-like and metalloprotease with thrombospondin type 1 motif 13 (ADAMTS13) and interleukin 6 in patients with acute myeloid leukaemia.European journal of medical research · 2025Trial
- Pediatric acute myeloid leukemia tumor composition predicts patient outcomes at diagnosis and reveals mechanisms of resistance to chemotherapy.Research square · 2026Article
- Characterization of Chemoresistant Cell Populations Improves Risk Stratification and Therapy Prediction in Pediatric AML.bioRxiv : the preprint server for biology · 2025Article
- Targeted inhibition of the PI3K/AKT/mTOR pathway by (+)-anthrabenzoxocinone induces cell cycle arrest, apoptosis, and autophagy in non-small cell lung cancer.Cellular & molecular biology letters · 2024Article
- Hypoxia-initiated Cysteine-rich protein 61 secretion promotes chemoresistance of acute B lymphoblastic leukemia cells.American journal of cancer research · 2024Article
- An Updated Overview of the Role of CYP450 during Xenobiotic Metabolization in Regulating the Acute Myeloid Leukemia Microenvironment.International journal of molecular sciences · 2023Review
- Article
- DNA damage to bone marrow stromal cells by antileukemia drugs induces chemoresistance in acute myeloid leukemia via paracrine FGF10-FGFR2 signaling.The Journal of biological chemistry · 2023Article
- Targeting the Tumor Microenvironment in Acute Myeloid Leukemia: The Future of Immunotherapy and Natural Products.Biomedicines · 2022Review
- Defining the transcriptional control of pediatric AML highlights RARA as a superenhancer-regulated druggable dependency.Blood advances · 2021Article
- Primary mesenchymal stromal cells in co-culture with leukaemic HL-60 cells are sensitised to cytarabine-induced genotoxicity, while leukaemic cells are protected.Mutagenesis · 2021Article
- 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
- CCN2 (Cellular Communication Network factor 2) in the bone marrow microenvironment, normal and malignant hematopoiesis.Journal of cell communication and signaling · 2021Review
- PAK1 Mediates Bone Marrow Stromal Cell-Induced Drug Resistance in Acute Myeloid Leukemia via ERK1/2 Signaling Pathway.Frontiers in cell and developmental biology · 2021Article
- Cyr61 mediates oxaliplatin resistance in colorectal cancer cells by regulating Bcl-xL expression.Journal of Cancer · 2021Article
- Atovaquone is active against AML by upregulating the integrated stress pathway and suppressing oxidative phosphorylation.Blood advances · 2019Article
- Cysteine-rich protein 61 regulates the chemosensitivity of chronic myeloid leukemia to imatinib mesylate through the nuclear factor kappa B/Bcl-2 pathway.Cancer science · 2019Article
- Inhibition of CYR61-S100A4 Axis Limits Breast Cancer Invasion.Frontiers in oncology · 2019Article
- MiR-634 sensitizes glioma cells to temozolomide by targeting CYR61 through Raf-ERK signaling pathway.Cancer medicine · 2018Article
- Quercetin Suppresses CYR61-Mediated Multidrug Resistance in Human Gastric Adenocarcinoma AGS Cells.Molecules (Basel, Switzerland) · 2018Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
Approximately 50% of children with acute myeloid leukaemia (AML) relapse, despite aggressive chemotherapy. The bone marrow stromal environment protects leukaemia cells from chemotherapy (i.e., stroma-induced chemoresistance), eventually leading to recurrence. Our goal is to delineate the mechanisms underlying stroma-mediated chemoresistance in AML. We used two human bone marrow stromal cell lines, HS-5 and HS-27A, which are equally effective in protecting AML cells from chemotherapy-induced apoptosis in AML-stromal co-cultures. We found that CYR61 was highly expressed by stromal cells, and was upregulated in AML cells by both stromal cell lines. CYR61 is a secreted matricellular protein and is associated with cell-intrinsic chemoresistance in other malignancies. Here, we show that blocking stromal CYR61 activity, by neutralization or RNAi, increased mitoxantrone-induced apoptosis in AML cells in AML-stromal co-cultures, providing functional evidence for its role in stroma-mediated chemoresistance. Further, we found that spleen tyrosine kinase (SYK) mediates CYR61 signalling. Exposure to stroma increased SYK expression and activation in AML cells, and this increase required CYR61. SYK inhibition reduced stroma-dependent mitoxantrone resistance in the presence of CYR61, but not in its absence. Therefore, SYK is downstream of CYR61 and contributes to CYR61-mediated mitoxantrone resistance. The CYR61-SYK pathway represents a potential target for reducing stroma-induced chemoresistance.
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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.