1. ¹Centre National de la Recherche Scientifique, UMR8125, Institut Gustave Roussy, 39 rue Camille-Desmoulins, F-94805 Villejuif, France
2. ²Hematology Unit, Hôpital Avicenne, AP-HP, Université Paris 13, F-93000 Bobigny, France

Correspondence: G Kroemer, Centre National de la Recherche Scientifique, UMR8125, Institut Gustave Roussy, PR1, 39 rue Camille Desmoulins, F-94805 Villejuif, France. Tel: +33 1 42 11 60 46; Fax: +33 1 42 11 60 47; E-mail: kroemer@igr.fr

Received 25 October 2005; Revised 7 December 2005; Accepted 23 December 2005; Published online 24 February 2006.

Abstract

The transcription factor nuclear factor kappa B (NF-B) can intervene in oncogenesis by virtue of its capacity to regulate the expression of a plethora of genes that modulate apoptosis, and cell survival as well as proliferation, inflammation, tumor metastasis and angiogenesis. Different reports demonstrate the intrinsic activation of NF-B in lymphoid and myeloid malignancies, including preneoplastic conditions such as myelodysplastic syndromes, underscoring its implication in malignant transformation. Targeting intrinsic NF-B activation, as well as its upstream and downstream regulators, may hence constitute an additional approach to the oncologist's armamentarium. Several small inhibitors of the NF-B-activatory kinase IB kinase, of the proteaseome, or of the DNA binding of NF-B subunits are under intensive investigation. Currently used cytotoxic agents can induce NF-B activation as an unwarranted side effect, which confers apoptosis suppression and hence resistance to these drugs. Thus, NF-B inhibitory molecules may be clinically useful, either as single therapeutic agents or in combination with classical chemotherapeutic agents, for the treatment of hematological malignancies.