Role of GSTP1-1 in mediating the effect of As2O3 in the Acute Promyelocytic Leukemia cell line NB4.


:Arsenic trioxide (As2O3) is a highly effective agent in the treatment of acute promyelocytic leukemia (APL), whereas other hematopoietic tumors are less responsive to this agent and mechanisms underlying As2O3,-resistance are poorly understood. To better understand the complex network of GSH-related pathways in As2O3 sensitivity, we investigated the role of GSH and GSH-relevant enzymes in an APL cell line sensitive to As2O3 (NB4) and in a resistant subclone (AsR). Cell proliferation, viability, and apoptosis were investigated in NB4 cells before and after treatment with 1 muM As2O3 and in AsR cells. In these experimental cell models, GSTP1-1, JNK1 and JNK2 proteins were analyzed by immunoblotting, and a kinase assay for JNK1 was performed. GSH levels as well as the activities of the enzymes glutathione peroxidase, glutathione transferase, gamma-Glutamylcysteynilsinthetase and superoxide dismutase were measured. NB4 cells treated with As2O3 showed a high level of oxidative stress and an increase of GSH levels. GSTP1-1 polymerization and JNK1 activation were detectable after 24 h and were followed by an increase of the apoptotic rate starting at 72 h. Neither GSTP1-1 polymerization nor JNK activation was found in AsR cells that showed a very low apoptotic rate. Our results suggest that APL sensitivity to As2O3 might be, at least in part, mediated by the balance between association and dissociation of JNK from GSTP1-1, depending on the redox status of the cell. Further investigation is warranted to find a way to interfere with this balance, whenever it might represent a mechanism of drug resistance.


Ann Hematol


Annals of hematology


Bernardini S,Nuccetelli M,Noguera NI,Bellincampi L,Lunghi P,Bonati A,Mann K,Miller WH Jr,Federici G,Lo Coco F




Has Abstract


2006-10-01 00:00:00












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  • High-dose therapy and stem cell transplantation in follicular lymphoma.

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    pub_type: 临床试验,杂志文章


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    更新日期:2020-03-01 00:00:00

  • Prognostic value of cytogenetics in adult patients with Philadelphia-negative acute lymphoblastic leukemia.

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    更新日期:2004-03-01 00:00:00

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  • Allogeneic bone marrow transplantation compared to peripheral blood stem cell transplantation for the treatment of hematologic malignancies: a meta-analysis based on time-to-event data from randomized controlled trials.

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    pub_type: 杂志文章


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    pub_type: 临床试验,杂志文章


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    pub_type: 临床试验,杂志文章


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    更新日期:2017-12-01 00:00:00

  • Platelet activation and function during eltrombopag treatment in immune thrombocytopenia.

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    journal_title:Annals of hematology

    pub_type: 杂志文章,随机对照试验


    authors: Haselboeck J,Pabinger I,Ay C,Koder S,Panzer S

    更新日期:2012-01-01 00:00:00

  • The role of cytokines and hematopoietic growth factors in the autocrine/paracrine regulation of inducible hematopoiesis.

    abstract::To elucidate the role of hematopoietic growth factors (HGFs) and other cytokines in the autocrine or paracrine regulation of inducible hematopoiesis we studied cytokine gene expression in the bone marrow (BM) of patients after myelosuppressive treatment. Furthermore, we studied the cytokine gene expression profile in ...

    journal_title:Annals of hematology

    pub_type: 杂志文章


    authors: Cluitmans FH,Esendam BH,Veenhof WF,Landegent JE,Willemze R,Falkenburg JH

    更新日期:1997-07-01 00:00:00