Journal
LEUKEMIA RESEARCH
Volume 33, Issue 7, Pages 924-928Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.leukres.2009.01.027
Keywords
Unfolded protein response; Bcr-Abl; Apoptosis
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Funding
- Ministry of Education, Culture, Sports, Science and Technology, Japan
- UBE Kosan Foundation
- and Yamaguchi University Foundation
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To define the role of the unfolded protein response (UPR) in leukemogenesis, we investigated UPR activation in the cells expressing the representative oncogene Bcr-Abl (B-A). The expression of UPR-related proteins and mRNAs, namely, X-box-binding protein (XBP1) and glucose-regulated protein 78 (GRP78) was increased in B-A. UPR inhibition using inositol-requiring enzyme 1 alpha (IRE1 alpha) or activating transcription factor 6 (ATF6) dominant-negative mutants diminished the ability of Bcr-Abl to protect the cells from etoposide- and imatinib-induced apoptosis. We also noted that the expression of UPR-related genes in primary leukemia cells from Philadelphia chromosome (Ph)-positive cells was higher than that in the control by quantitative RT-PCR assay Thus, our results suggested that UPR is a downstream target of Bcr-Abl and plays an anti-apoptotic role in Ph-positive leukemia cells. (C) 2009 Elsevier Ltd. All rights reserved.
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