Journal
LEUKEMIA
Volume 20, Issue 5, Pages 800-806Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/sj.leu.2404167
Keywords
CLL; NF-kappa B; apoptosis; DHMEQ; fludarabine
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Chronic lymphocytic leukemia (CLL) is a low-grade lymphoid malignancy incurable with conventional modalities of chemotherapy. Strong and constitutive nuclear factor kappa B (NF-kappa B) activation is a characteristic of CLL cells. We examined the effects of a new NF-kappa B inhibitor, dehydroxymethylepoxyquinomicin (DHMEQ), on CLL cells. Dehydroxymethylepoxyquinomicin completely abrogated constitutive NF-kappa B activity and induced apoptosis of CLL cells. Apoptosis induced by DHMEQ was accompanied by downregulation of NF-kappa B-dependent antiapoptotic genes: c-lAP, Bfl-1, Bcl-X-L and c-FLIP. Dehydroxymethylepoxyquinomicin also inhibited NF-kappa B induced by CD40 and enhanced fludarabine-mediated apoptosis of CLL cells. Results of this study suggest that inhibition of constitutive and inducible NF-kappa B by DHMEQ in combination with fludarabine is a promising strategy for the treatment of CLL.
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