ArticleLeukemia2019
NG2 antigen is a therapeutic target for MLL-rearranged B-cell acute lymphoblastic leukemia.
Article in Leukemia, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 49 citations in OpenAlex.
- Allogeneic Hematopoietic Stem Cell Transplantation for Infant Leukemia: A Single-Center Case Series and Narrative Review.Children (Basel, Switzerland) · 2025Review
- Review
- HDAC7 induction combined with standard-of-care chemotherapy provides a therapeutic advantage in t(4;11) infant B-cell acute lymphoblastic leukemia.Biomarker research · 2025Article
- A translational perspective of the malignant hematopoietic proteoglycome.Cell & bioscience · 2025Review
- Transcriptome analysis of primary adult B-cell lineage acute lymphoblastic leukemia identifies pathogenic variants and gene fusions, and predicts subtypes for in depth molecular diagnosis.European journal of haematology · 2024Article
- Aberrant stem cell and developmental programs in pediatric leukemia.Frontiers in cell and developmental biology · 2024Review
- Chromosomal instability in aneuploid acute lymphoblastic leukemia associates with disease progression.EMBO molecular medicine · 2024Article
- NG2 Molecule Expression in Acute Lymphoblastic Leukemia B Cells: A Flow-Cytometric Marker for the Rapid Identification ofMediterranean journal of hematology and infectious diseases · 2024Article
- The Philadelphia Chromosome, from Negative to Positive: A Case Report of Relapsed Acute Lymphoblastic Leukemia Following Allogeneic Stem Cell Transplantation.Medicina (Kaunas, Lithuania) · 2023Article
- Updates inBiomedicines · 2023Review
- Updates in infant acute lymphoblastic leukemia and the potential for targeted therapy.Hematology. American Society of Hematology. Education Program · 2022Article
- LAMP-5 is an essential inflammatory-signaling regulator and novel immunotherapy target for mixed lineage leukemia-rearranged acute leukemia.Haematologica · 2022Article
- The Multi-Kinase Inhibitor EC-70124 Is a Promising Candidate for the Treatment of FLT3-ITD-Positive Acute Myeloid Leukemia.Cancers · 2022Article
- A human fetal liver-derived infant MLL-AF4 acute lymphoblastic leukemia model reveals a distinct fetal gene expression program.Nature communications · 2021Article
- Integrative methylome-transcriptome analysis unravels cancer cell vulnerabilities in infant MLL-rearranged B cell acute lymphoblastic leukemia.The Journal of clinical investigation · 2021Article
- Subgrouping by gene expression profiles to improve relapse risk prediction in paediatric B-precursor acute lymphoblastic leukaemia.Cancer medicine · 2021Article
- Glycoproteome remodeling in MLL-rearranged B-cell precursor acute lymphoblastic leukemia.Theranostics · 2021Article
- Article
- HOXA9/IRX1 expression pattern defines two subgroups of infant MLL-AF4-driven acute lymphoblastic leukemia.Experimental hematology · 2021Article
- Challenges and Clinical Strategies of CAR T-Cell Therapy for Acute Lymphoblastic Leukemia: Overview and Developments.Frontiers in immunology · 2020Review
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Authors and funding
13 authors at 5 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
B cell acute lymphoblastic leukemia (B-ALL) is the most common childhood cancer, with cure rates of ∼80%. MLL-rearranged (MLLr) B-ALL (MLLr-B-ALL) has, however, an unfavorable prognosis with common therapy refractoriness and early relapse, and therefore new therapeutic targets are needed for relapsed/refractory MLLr-B-ALL. MLLr leukemias are characterized by the specific expression of chondroitin sulfate proteoglycan-4, also known as neuron-glial antigen-2 (NG2). NG2 was recently shown involved in leukemia invasiveness and central nervous system infiltration in MLLr-B-ALL, and correlated with lower event-free survival (EFS). We here hypothesized that blocking NG2 may synergize with established induction therapy for B-ALL based on vincristine, glucocorticoids, and L-asparaginase (VxL). Using robust patient-derived xenograft (PDX) models, we found that NG2 is crucial for MLLr-B-ALL engraftment upon intravenous (i.v.) transplantation. In vivo blockade of NG2 using either chondroitinase-ABC or an anti-NG2-specific monoclonal antibody (MoAb) resulted in a significant mobilization of MLLr-B-ALL blasts from bone marrow (BM) to peripheral blood (PB) as demonstrated by cytometric and 3D confocal imaging analysis. When combined with either NG2 antagonist, VxL treatment achieved higher rates of complete remission, and consequently higher EFS and delayed time to relapse. Mechanistically, anti-NG2 MoAb induces neither antibody-dependent cell-mediated not complement-dependent cytotoxicity. NG2 blockade rather overrides BM stroma-mediated chemoprotection through PB mobilization of MLLr-B-ALL blasts, thus becoming more accessible to chemotherapy. We provide a proof of concept for NG2 as a therapeutic target for MLLr-B-ALL.
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