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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
biochemistry, genetics and molecular biology
Arsenic/interferon specifically reverses 2 distinct gene networks critical for the survival of HTLV-1-infected leukemic cells
Blood, Volume 101, No. 11, Year 2003
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Description
Adult T-cell leukemia (ATL) is a severe chemotherapy-resistant malignancy associated with prolonged infection by the human T cell-lymphotropic virus 1 (HTLV-1) retrovirus. Although the Tax viral transactivator is clearly an oncogene, the role of its continuous expression in the maintenance of the transformed phenotype is controversial. Because arsenic trioxide (As) and interferon α (IFN) synergize to induce cell cycle arrest and apoptosis of ATL cells both ex vivo and in vitro, we investigated the effects of As alone and As/IFN combination on gene networks in HTLV-1-infected leukemic cells. The As/IFN combination reduced Tax expression and, accordingly, reversed the Tax-induced constitutive nuclear factor κB (NF-κB) activation. Using DNA microarray analyses, we demonstrated that As rapidly and selectively blocks the transcription of NF-κB-dependent genes in HTLV-1-infected cells only. Reversal of NF-κB activation by As alone resulted from dramatic stabilization of IκB-α and IκB-ε, independently of IκB kinase (IKK) activity modulation or Tax degradation. In contrast, only the As/IFN combination induced late and massive down-regulation of cell cycle-regulated genes, concomitantly with Tax degradation by the proteasome and cell death induction, indicating the importance of continuous Tax expression for ATL cell survival. These 2 successive events likely account for the potent and specific effects of the As/IFN combination in ATL. © 2003 by The American Society of Hematology.
Authors & Co-Authors
Nasr, Rihab
Unknown Affiliation
Rosenwald, Andreas R.
Unknown Affiliation
El-Sabban, Marwan
Unknown Affiliation
Arnulf, Bertrand
Unknown Affiliation
Zalloua, Pierre A.
Unknown Affiliation
Lepelletier, Yves
Unknown Affiliation
Bex, Françoise
Unknown Affiliation
Hermine, Olivier
Unknown Affiliation
Staudt, Louis M.
Unknown Affiliation
de Thȩ, Hugues B.
France, Paris
Hôpital Saint-louis
Bazarbachi, Ali Abdul Hamid
Lebanon, Beirut
American University of Beirut
Statistics
Citations: 108
Authors: 11
Affiliations: 2
Identifiers
Doi:
10.1182/blood-2002-09-2986
ISSN:
00064971
Research Areas
Cancer
Genetics And Genomics