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BCR-ABL mediates arsenic trioxide-induced apoptosis independently of its aberrant kinase activity.
Cancer Res 2000; 60(13):3409-13CR

Abstract

In the prechemotherapy era arsenic derivatives were used for treatment of chronic myelogenous leukemia, a myeloproliferative disorder characterized by the t(9;22) translocation, the Philadelphia chromosome (Ph+). In acute promyelocytic leukemia response to arsenic trioxide (As2O3) has been shown to be genetically determined by the acute promyelocytic leukemia-specific t(15;17) translocation product PML/RARalpha. Hence, we reasoned that As2O3 might have a selective inhibitory effect on proliferation of BCR-ABL-expressing cells. Here, we report that: (a) As2O3 induced apoptosis in Ph+ but not in Ph- lymphoblasts; (b) enforced expression of BCR-ABL in U937 cells dramatically increased the sensitivity to As2O3; (c) the effect of As2O3 was independent of BCR-ABL kinase activity; and (d) As2O3 reduced proliferation of chronic myelogenous leukemia blasts but not of peripheral CD34+ progenitors. In summary, these data establish As2O3 as a tumor cell-specific agent, making its clinical application in Ph+ leukemia feasible.

Authors+Show Affiliations

Medizinische Klinik III/Abteilung Hämatologie, Johann Wolfgang Goethe-Universität, Frankfurt, Germany.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

10910048

Citation

Puccetti, E, et al. "BCR-ABL Mediates Arsenic Trioxide-induced Apoptosis Independently of Its Aberrant Kinase Activity." Cancer Research, vol. 60, no. 13, 2000, pp. 3409-13.
Puccetti E, Güller S, Orleth A, et al. BCR-ABL mediates arsenic trioxide-induced apoptosis independently of its aberrant kinase activity. Cancer Res. 2000;60(13):3409-13.
Puccetti, E., Güller, S., Orleth, A., Brüggenolte, N., Hoelzer, D., Ottmann, O. G., & Ruthardt, M. (2000). BCR-ABL mediates arsenic trioxide-induced apoptosis independently of its aberrant kinase activity. Cancer Research, 60(13), pp. 3409-13.
Puccetti E, et al. BCR-ABL Mediates Arsenic Trioxide-induced Apoptosis Independently of Its Aberrant Kinase Activity. Cancer Res. 2000 Jul 1;60(13):3409-13. PubMed PMID: 10910048.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - BCR-ABL mediates arsenic trioxide-induced apoptosis independently of its aberrant kinase activity. AU - Puccetti,E, AU - Güller,S, AU - Orleth,A, AU - Brüggenolte,N, AU - Hoelzer,D, AU - Ottmann,O G, AU - Ruthardt,M, PY - 2000/7/26/pubmed PY - 2000/8/19/medline PY - 2000/7/26/entrez SP - 3409 EP - 13 JF - Cancer research JO - Cancer Res. VL - 60 IS - 13 N2 - In the prechemotherapy era arsenic derivatives were used for treatment of chronic myelogenous leukemia, a myeloproliferative disorder characterized by the t(9;22) translocation, the Philadelphia chromosome (Ph+). In acute promyelocytic leukemia response to arsenic trioxide (As2O3) has been shown to be genetically determined by the acute promyelocytic leukemia-specific t(15;17) translocation product PML/RARalpha. Hence, we reasoned that As2O3 might have a selective inhibitory effect on proliferation of BCR-ABL-expressing cells. Here, we report that: (a) As2O3 induced apoptosis in Ph+ but not in Ph- lymphoblasts; (b) enforced expression of BCR-ABL in U937 cells dramatically increased the sensitivity to As2O3; (c) the effect of As2O3 was independent of BCR-ABL kinase activity; and (d) As2O3 reduced proliferation of chronic myelogenous leukemia blasts but not of peripheral CD34+ progenitors. In summary, these data establish As2O3 as a tumor cell-specific agent, making its clinical application in Ph+ leukemia feasible. SN - 0008-5472 UR - https://www.unboundmedicine.com/medline/citation/10910048/BCR_ABL_mediates_arsenic_trioxide_induced_apoptosis_independently_of_its_aberrant_kinase_activity_ L2 - http://cancerres.aacrjournals.org/cgi/pmidlookup?view=long&pmid=10910048 DB - PRIME DP - Unbound Medicine ER -