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Publication Detail
NF-κB activation mediates resistance to IFNΒ in MLL-rearranged acute lymphoblastic leukemia
  • Publication Type:
    Journal article
  • Publication Sub Type:
    Journal Article
  • Authors:
    Tracey L, Streck CJ, Du Z, Williams RF, Pfeffer LM, Nathwani AC, Davidoff AM
  • Publication date:
  • Pagination:
    806, 812
  • Journal:
  • Volume:
  • Issue:
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  • Print ISSN:
Acute lymphoblastic leukemia (ALL) harboring the t(4;11) translocation is associated with a very poor prognosis; innovative treatment strategies are required to improve the current 5-year survival rate of 30-40%. Interferon Β (IFNΒ) has shown promise in the treatment of both solid and hematologic malignancies, although the short half-life and toxicity associated with high doses have limited its clinical utility. To overcome these limitations, we investigated the effect of continuous, gene transfer-mediated delivery of IFNΒ using adeno-associated virus (AAV)-mediated expression, on ALL cells with the t(4;11) translocation. We found that this method of IFNΒ delivery resulted in complete remission of leukemia in a murine model. However, leukemic cells eventually became resistant to IFNΒ and relapse was observed. Activation of NF-B was identified as a mechanism for IFNΒ resistance, and inhibition of NF-B activity in resistant cells sensitized cells to IFNΒ. IFNΒ combined with agents that inhibit NF-B could have therapeutic potential in the treatment of children with mixed lineage leukemia subtype ALL. © 2010 Macmillan Publishers Limited All rights reserved.
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