ArticleCancer research2018
A Novel Germline Variant in CSF3R Reduces N-Glycosylation and Exerts Potent Oncogenic Effects in Leukemia.
Article in Cancer research, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 22 citations in OpenAlex.
- Research progress on the mechanisms of CSF3R mutations in leukemogenesis and treatment strategies.Cancer cell international · 2025Review
- Glycosylation: mechanisms, biological functions and clinical implications.Signal transduction and targeted therapy · 2024Review
- A novel colony stimulating factor 3 receptor activating mutation identified in a patient with chronic neutrophilic leukemia.Haematologica · 2023Article
- Extremely rare chronic neutrophilic leukemia characterized by unrelieved abdominal distention and swollen painful limbs: new clinical insight.American journal of translational research · 2023Article
- Profiling the Bisecting N-acetylglucosamine Modification in Amniotic Membrane via Mass Spectrometry.Genomics, proteomics & bioinformatics · 2022Article
- Seeing the forest through the trees: characterizing the glycoproteome.Trends in biochemical sciences · 2022Review
- Co-Occurring CSF3R W791* Germline and Somatic T618I Driver Mutations Induce Early CNL and Clonal Progression to Mixed Phenotype Acute Leukemia.Current oncology (Toronto, Ont.) · 2022Article
- Novel Insights into the Prognosis and Immunological Value of the SLC35A (Solute Carrier 35A) Family Genes in Human Breast Cancer.Biomedicines · 2021Article
- Clinical utility of targeted next-generation sequencing for the diagnosis of myeloid neoplasms with germline predisposition.Molecular oncology · 2021Article
- Chronic Neutrophilic Leukemia: A Literature Review of the Rare Myeloproliferative Pathology.Cureus · 2021Review
- Current Methods of Post-Translational Modification Analysis and Their Applications in Blood Cancers.Cancers · 2021Review
- The clinical impact of glycobiology: targeting selectins, Siglecs and mammalian glycans.Nature reviews. Drug discovery · 2021Review
- When Glycosylation Meets Blood Cells: A Glance of the Aberrant Glycosylation in Hematological Malignancies.Reviews of physiology, biochemistry and pharmacology · 2021Review
- Effective treatment of progressive nodular histiocytosis by intermediate-dose cytarabine: a case report and literature review.American journal of translational research · 2021Article
- Heterozygous germ line CSF3R variants as risk alleles for development of hematologic malignancies.Blood advances · 2020Article
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Authors and funding
13 authors at 8 institutions in 1 country.
Funding
Abstract
: Mutations in the colony-stimulating factor 3 receptor (CSF3R) have been identified in the vast majority of patients with chronic neutrophilic leukemia and are present in other kinds of leukemia, such as acute myeloid leukemia. Here, we studied the function of novel germline variants in CSF3R at amino acid N610. These N610 substitutions were potently oncogenic and activated the receptor independently of its ligand GCSF. These mutations activated the JAK-STAT signaling pathway and conferred sensitivity to JAK inhibitors. Mass spectrometry revealed that the N610 residue is part of a consensus N-linked glycosylation motif in the receptor, usually linked to complex glycans. N610 was also the primary site of sialylation of the receptor. Membrane-proximal N-linked glycosylation was critical for maintaining the ligand dependence of the receptor. Mutation of the N610 site prevented membrane-proximal N-glycosylation of CSF3R, which then drove ligand-independent cellular expansion. Kinase inhibitors blocked growth of cells with an N610 mutation. This study expands the repertoire of oncogenic mutations in CSF3R that are therapeutically targetable and provides insight into the function of glycans in receptor regulation. SIGNIFICANCE: This study reveals the critical importance of membrane-proximal N-linked glycosylation of CSF3R for the maintenance of ligand dependency in leukemia.
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