ArticleThe Journal of clinical investigation2014
SPARC promotes leukemic cell growth and predicts acute myeloid leukemia outcome.
Article in The Journal of clinical investigation, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers, 1 of them a synthesis that pooled it.
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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
31 citing papers in PubMed, 1 synthesis or guideline pooled it, 58 citations in OpenAlex.
- The M2 macrophage markerOncoimmunology · 2020Pooled it
- SPARC Promotes Corneal Epithelial Wound Healing Through β-catenin Nuclear Translocation and c-Met Activation.Investigative ophthalmology & visual science · 2026Article
- Regulatory Mechanisms of SPARC Overexpression in Melanoma Progression.International journal of molecular sciences · 2025Article
- SPARC Induces COL1A1/COL3A1 Expressions Representing Aggressive Molecular Cancer-Associated Fibroblasts Signatures and CSF1-Mediated Cancer Invasion in Colorectal Cancer.Annals of surgical oncology · 2025Article
- A Single Intraperitoneal Secreted Protein Acidic and Rich in Cysteine Injection in Mice Is Towards an Exercise-like Phenotype.Biology · 2025Article
- Tumor-secreted LCN2 impairs gastric cancer progression via autocrine inhibition of the 24p3R/JNK/c-Jun/SPARC axis.Cell death & disease · 2024Article
- CAFs-Associated Genes (CAFGs) in Pancreatic Ductal Adenocarcinoma (PDAC) and Novel Therapeutic Strategy.International journal of molecular sciences · 2024Review
- GP60 and SPARC as albumin receptors: key targeted sites for the delivery of antitumor drugs.Frontiers in pharmacology · 2024Review
- Secreted Protein Acidic and Rich in Cysteine (Metabolites · 2022Article
- Article
- Clinical Proteomics of Biofluids in Haematological Malignancies.International journal of molecular sciences · 2021Review
- SPARC promotes pancreatic cancer cell proliferation and migration through autocrine secretion into the extracellular milieu.Oncology letters · 2021Article
- Single-cell expression and Mendelian randomization analyses identify blood genes associated with lifespan and chronic diseases.Communications biology · 2020Article
- Sparse multiple co-Inertia analysis with application to integrative analysis of multi -Omics data.BMC bioinformatics · 2020Article
- Genetic variant ofArchives animal breeding · 2020Article
- CD97 expression is associated with poor overall survival in acute myeloid leukemia.Experimental hematology · 2019Article
- Linking NRP2 With EMT and Chemoradioresistance in Bladder Cancer.Frontiers in oncology · 2019Article
- iTRAQ-based quantitative protein expression profiling of biomarkers in childhood B-cell and T-cell acute lymphoblastic leukemia.Cancer management and research · 2019Article
- Altered CSF Proteomic Profiling of Paediatric Acute Lymphocytic Leukemia Patients with CNS Infiltration.Journal of oncology · 2019Article
- CRISPR/Cas9-edited NSG mice as PDX models of human leukemia to address the role of niche-derived SPARC.Leukemia · 2018Article
Corrections and comments
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Authors and funding
31 authors at 6 institutions in 1 country.
Funding
Abstract
Aberrant expression of the secreted protein, acidic, cysteine-rich (osteonectin) (SPARC) gene, which encodes a matricellular protein that participates in normal tissue remodeling, is associated with a variety of diseases including cancer, but the contribution of SPARC to malignant growth remains controversial. We previously reported that SPARC was among the most upregulated genes in cytogenetically normal acute myeloid leukemia (CN-AML) patients with gene-expression profiles predictive of unfavorable outcome, such as mutations in isocitrate dehydrogenase 2 (IDH2-R172) and overexpression of the oncogenes brain and acute leukemia, cytoplasmic (BAALC) and v-ets erythroblastosis virus E26 oncogene homolog (ERG). In contrast, SPARC was downregulated in CN-AML patients harboring mutations in nucleophosmin (NPM1) that are associated with favorable prognosis. Based on these observations, we hypothesized that SPARC expression is clinically relevant in AML. Here, we found that SPARC overexpression is associated with adverse outcome in CN-AML patients and promotes aggressive leukemia growth in murine models of AML. In leukemia cells, SPARC expression was mediated by the SP1/NF-κB transactivation complex. Furthermore, secreted SPARC activated the integrin-linked kinase/AKT (ILK/AKT) pathway, likely via integrin interaction, and subsequent β-catenin signaling, which is involved in leukemia cell self-renewal. Pharmacologic inhibition of the SP1/NF-κB complex resulted in SPARC downregulation and leukemia growth inhibition. Together, our data indicate that evaluation of SPARC expression has prognosticative value and SPARC is a potential therapeutic target for AML.
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Registered trials
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