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. 2006 Oct;30(10):1263-72.
doi: 10.1016/j.leukres.2006.01.005. Epub 2006 Feb 14.

Adaphostin and bortezomib induce oxidative injury and apoptosis in imatinib mesylate-resistant hematopoietic cells expressing mutant forms of Bcr/Abl

Girija Dasmahapatra  1 , Tri K Nguyen, Paul Dent, Steven Grant
Affiliations

Adaphostin and bortezomib induce oxidative injury and apoptosis in imatinib mesylate-resistant hematopoietic cells expressing mutant forms of Bcr/Abl

Girija Dasmahapatra et al. Leuk Res. 2006 Oct.

Erratum in

Abstract

Effects of the tyrphostin adaphostin and bortezomib were examined in Bcr/Abl+ leukemia cell resistant to imatinib mesylate secondary to Bcr/Abl point mutations. Adaphostin was equally effective in inducing mitochondrial damage, caspase activation, JNK activation, and Raf-1, phospho-Stat3 and -Stat5 inactivation in mutant and wild-type cells, but differentially down-regulated phospho-Bcr/Abl. Adaphostin and bortezomib synergistically induced apoptosis in wild-type and mutant cells, including T315I mutants. Notably, adaphostin+/-bortezomib potently induced ROS and lethality in mutant cells, effects attenuated by the antioxidant NAC. These findings indicate that adaphostin+/-bortezomib circumvent imatinib resistance due to Bcr/Abl point mutations most likely through ROS generation.

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  • Findings of Research Misconduct.
    [No authors listed] [No authors listed] NIH Guide Grants Contracts (Bethesda). 2015 Dec 18:NOT-OD-16-040. NIH Guide Grants Contracts (Bethesda). 2015. PMID: 26693581 Free PMC article. No abstract available.
  • Findings of Research Misconduct.
    [No authors listed] [No authors listed] Fed Regist. 2015 Dec 10;80(237):76703-76704. Fed Regist. 2015. PMID: 27737268 Free PMC article. No abstract available.

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