ArticleNeoplasia (New York, N.Y.)2008
Resistance to cytarabine induces the up-regulation of NKG2D ligands and enhances natural killer cell lysis of leukemic cells.
Article in Neoplasia (New York, N.Y.), 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 41 citations in OpenAlex.
- Development of Chimeric Antigen Receptor-Modified NK Cells for the Immunotherapy of Adult T-Cell Leukemia/Lymphoma.European journal of haematology · 2026Article
- FT538, iPSC-derived NK cells, enhance AML cell killing when combined with chemotherapy.Journal of cellular and molecular medicine · 2025Article
- Review
- Bortezomib enhances cytotoxicity of ex vivo-expanded gamma delta T cells against acute myeloid leukemia and T-cell acute lymphoblastic leukemia.Cytotherapy · 2021Article
- BRAF inhibitor resistance of melanoma cells triggers increased susceptibility to natural killer cell-mediated lysis.Journal for immunotherapy of cancer · 2020Article
- Improving the Clinical Application of Natural Killer Cells by Modulating Signals Signal from Target Cells.International journal of molecular sciences · 2019Article
- NKG2D/NKG2-Ligand Pathway Offers New Opportunities in Cancer Treatment.Frontiers in immunology · 2019Review
- Article
- Silencing NKG2D ligand-targeting miRNAs enhances natural killer cell-mediated cytotoxicity in breast cancer.Cell death & disease · 2017Article
- Biological evaluation of both enantiomers of fluoro-thalidomide using human myeloma cell line H929 and others.PloS one · 2017Article
- NK cell activating receptor ligand expression in lymphangioleiomyomatosis is associated with lung function decline.JCI insight · 2016Article
- Article
- Article
- Valproic acid upregulates NKG2D ligand expression through an ERK-dependent mechanism and potentially enhances NK cell-mediated lysis of myeloma.Neoplasia (New York, N.Y.) · 2012Article
- Differential gene expression in motor and sensory Schwann cells in the rat femoral nerve.Journal of neuroscience research · 2012Article
- Dinosaurs and ancient civilizations: reflections on the treatment of cancer.Neoplasia (New York, N.Y.) · 2010Article
- Tumor cells infected with oncolytic influenza A virus prime natural killer cells for lysis of resistant tumor cells.Medical microbiology and immunology · 2010Article
- The War on Cancer rages on.Neoplasia (New York, N.Y.) · 2009Article
- Chemoresistance acquisition induces a global shift of expression of aniogenesis-associated genes and increased pro-angogenic activity in neuroblastoma cells.Molecular cancer · 2009Article
- Neoplasia: the second decade.Neoplasia (New York, N.Y.) · 2008Article
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Prolonged treatment of leukemic cells with chemotherapeutic agents frequently results in development of drug resistance. Moreover, selection of drug-resistant cell populations may be associated with changes in malignant properties such as proliferation rate, invasiveness, and immunogenicity. In the present study, the sensitivity of cytarabine (1-beta-D-arabinofuranosylcytosine, araC)-resistant and parental human leukemic cell lines (T-lymphoid H9 and acute T-lymphoblastic leukemia Molt-4) to natural killer (NK) cell-mediated killing was investigated. The results obtained demonstrate that araC-resistant H9 and Molt-4 (H9(r)ARAC(100) and Molt-4(r)ARAC(100)) cell lines are more sensitive to NK cell-mediated lysis than their respective parental cell lines. This increased sensitivity was associated with a higher surface expression of ligands for the NK cell-activating receptor NKG2D, notably UL16 binding protein-2 (ULBP-2) and ULBP-3 in H9(r)ARAC(100) and Molt-4(r)ARAC(100) cell lines. Blocking ULBP-2 and ULBP-3 or NKG2D with monoclonal antibody completely abrogated NK cell lysis. Constitutive phosphorylated extracellular signal-regulated kinase (ERK) but not pAKT was higher in araC-resistant cells than in parental cell lines. Inhibition of ERK using ERK inhibitor PD98059 decreased both ULBP-2/ULBP-3 expression and NK cell cytotoxicity. Furthermore, overexpression of constitutively active ERK in H9 parental cells resulted in increased ULBP-2/ULBP-3 expression and enhanced NK cell lysis. These results demonstrate that increased sensitivity of araC-resistant leukemic cells to NK cell lysis is caused by higher NKG2D ligand expression, resulting from more active ERK signaling pathway.
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