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Cited by 344

The DOI matches its Crossref record; 1 of the 1 references it cites were found in a registry or an index.

Arsenic Trioxide as an Inducer of Apoptosis and Loss of PML/RARα Protein in Acute Promyelocytic Leukemia Cells

Open access
Shao, Wenlin, Fanelli, Mirco, Ferrara, Fabiana F., Riccioni, Roberta, Rosenauer, Angelika, Davison, Kelly, Lamph, William W., Waxman, Samuel, Pelicci, Pier Giuseppe, Lo Coco, Francesco, Avvisati, Giuseppe, Testy, Ugo, Peschle, Cesare, Gambacorti-Passerini, Carlo, Nervi, Clara, Miller, Wilson H.·1998·JNCI: Journal of the National Cancer Institute
DOI 10.1093/jnci/90.2.124
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Abstract

BACKGROUND: Retinoids, which are derivatives of vitamin A, induce differentiation of acute promyelocytic leukemia (APL) cells in vitro and in patients. However, APL cells develop resistance to retinoic acid treatment. Arsenic trioxide (As2O3) can induce clinical remission in patients with APL, including those who have relapsed after retinoic acid treatment, by inducing apoptosis (programmed cell death) of the leukemia cells. In this study, we investigated the molecular mechanisms by which As2O3 induces apoptosis in retinoic acid-sensitive NB4 APL cells, in retinoic acid-resistant derivatives of these cells, and in fresh leukemia cells from patients. METHODS: Apoptosis was assessed by means of DNA fragmentation analyses, TUNEL assays (i.e., deoxyuridine triphosphate labeling of DNA nicks with terminal deoxynucleotidyl transferase), and flow cytometry. Expression of the PML/RAR alpha fusion protein in leukemia cells was assessed by means of western blotting, ligand binding, and immunohistochemistry. Northern blotting and ribonuclease protection assays were used to evaluate changes in gene expression in response to retinoic acid and As2O3 treatment. RESULTS AND CONCLUSIONS: As2O3 induces apoptosis without differentiation in retinoic acid-sensitive and retinoic acid-resistant APL cells at concentrations that are achievable in patients. As2O3 induces loss of the PML/RAR alpha fusion protein in NB4 cells, in retinoic-acid resistant cells derived from them, in fresh APL cells from patients, and in non-APL cells transfected to express this protein. As2O3 and retinoic acid induce different patterns of gene regulation, and they inhibit the phenotypes induced by each other. Understanding the molecular basis of these differences in the effects of As2O3 and retinoic acid may guide the clinical use of arsenic compounds and provide insights into the management of leukemias that do not respond to retinoic acid.

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Metadata

Authors
Shao, W., Fanelli, M., Ferrara, F. F., Riccioni, R., Rosenauer, A., Davison, K., Lamph, W. W., Waxman, S., Pelicci, P. G., Lo Coco, F., Avvisati, G., Testy, U., Peschle, C., Gambacorti-Passerini, C., Nervi, C., & Miller, W. H.
Venue
JNCI: Journal of the National Cancer Institute
Publisher
Oxford University Press (OUP)
Published
1998-01-21
Volume
90
Issue
2
Pages
124-133
ISSN
  • 0027-8874 (ISSN-L)
  • 1460-2105
DOI
10.1093/jnci/90.2.124
OpenAlex
W2133935930
Cited by
344
References
1
FWCI
10.02
Type
journal article
Language
en
Open access
bronze

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CoChat. (2026). Citation check: Arsenic Trioxide as an Inducer of Apoptosis and Loss of PML/RARα Protein in Acute Promyelocytic Leukemia Cells. https://app.cochat.ai/papers/10.1093/jnci/90.2.124
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Shao, W., Fanelli, M., Ferrara, F. F., Riccioni, R., Rosenauer, A., Davison, K., Lamph, W. W., Waxman, S., Pelicci, P. G., Lo Coco, F., Avvisati, G., Testy, U., Peschle, C., Gambacorti-Passerini, C., Nervi, C., & Miller, W. H. (1998). Arsenic Trioxide as an Inducer of Apoptosis and Loss of PML/RARα Protein in Acute Promyelocytic Leukemia Cells. JNCI: Journal of the National Cancer Institute. https://doi.org/10.1093/jnci/90.2.124

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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).

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