TY - JOUR AU - Heiko Konig, AU - Nicolai Härtel, AU - Beate Schultheis, AU - Michael Schatz, AU - Christian Lorentz, AU - Junia V. Melo, AU - Rüdiger Hehlmann, AU - Andreas Hochhaus, AU - Paul La Rosée, PY - 2007/06/01 Y2 - 2024/03/29 TI - Enhanced Bcr-Abl-specific antileukemic activity of arsenic trioxide through glutathione-depletion in imatinib-resistant cells JF - Haematologica JA - haematol VL - 92 IS - 6 SE - Brief Reports DO - 10.3324/haematol.10955 UR - https://haematologica.org/article/view/4479 SP - 838-841 AB - 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. ER -