Enhanced Bcr-Abl-specific antileukemic activity of arsenic trioxide through glutathione-depletion in imatinib-resistant cells

Heiko Konig, Nicolai Härtel, Beate Schultheis, Michael Schatz, Christian Lorentz, Junia V. Melo, Rüdiger Hehlmann, Andreas Hochhaus, Paul La Rosée

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

The development of resistance to imatinib mesylate may partly depend on high Bcr-Abl-expression levels. Arsenic trioxide (ATO) has Bcr-Abl suppressing activity in vitro. Here we investigated means to improve ATO activity in CML by modulating cellular glutathione (GSH), a key regulator of ATO-activity in malignant disease. Our studies demonstrate that depletion of cellular glutathione using dl-buthionine-[S,R]-sulfoximine (BSO) enhances ATO activity against CML cells. GSH-depletion promotes enhanced Bcr-Abl specific activity of ATO through avid repression of Bcr-Abl protein levels and total cellular Bcr-Abl activity. These data provide a rationale for the clinical development of optimized ATO-based regimens through incorporation of GSH-modulators in CML treatment.

Original languageEnglish (US)
Pages (from-to)838-841
Number of pages4
JournalHaematologica
Volume92
Issue number6
DOIs
StatePublished - Jun 2007
Externally publishedYes

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Glutathione
Imatinib Mesylate
arsenic trioxide
Proteins

Keywords

  • Arsenic
  • Bcr-Abl
  • CML
  • Glutathione
  • Imatinib
  • Resistance

ASJC Scopus subject areas

  • Hematology

Cite this

Enhanced Bcr-Abl-specific antileukemic activity of arsenic trioxide through glutathione-depletion in imatinib-resistant cells. / Konig, Heiko; Härtel, Nicolai; Schultheis, Beate; Schatz, Michael; Lorentz, Christian; Melo, Junia V.; Hehlmann, Rüdiger; Hochhaus, Andreas; La Rosée, Paul.

In: Haematologica, Vol. 92, No. 6, 06.2007, p. 838-841.

Research output: Contribution to journalArticle

Konig, H, Härtel, N, Schultheis, B, Schatz, M, Lorentz, C, Melo, JV, Hehlmann, R, Hochhaus, A & La Rosée, P 2007, 'Enhanced Bcr-Abl-specific antileukemic activity of arsenic trioxide through glutathione-depletion in imatinib-resistant cells', Haematologica, vol. 92, no. 6, pp. 838-841. https://doi.org/10.3324/haematol.10955
Konig, Heiko ; Härtel, Nicolai ; Schultheis, Beate ; Schatz, Michael ; Lorentz, Christian ; Melo, Junia V. ; Hehlmann, Rüdiger ; Hochhaus, Andreas ; La Rosée, Paul. / Enhanced Bcr-Abl-specific antileukemic activity of arsenic trioxide through glutathione-depletion in imatinib-resistant cells. In: Haematologica. 2007 ; Vol. 92, No. 6. pp. 838-841.
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AU - Schatz, Michael

AU - Lorentz, Christian

AU - Melo, Junia V.

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