NF-κB as a potential therapeutic target in myelodysplastic syndromes and acute myeloid leukemia

Importance of the field: The inactive NF-kappa B-inhibitor of NF-kappa B (I kappa B) complex is activated by stimuli including pro-inflammatory cytokines, mitogens, growth factors and stress-inducing agents. The release of NF-kappa B facilitates its translocation to the nucleus, where it promotes cell survival by initiating transcription of genes encoding stress-response enzymes, cell-adhesion molecules, pro-inflammatory cytokines and anti-apoptotic proteins. NF-kappa B and associated regulatory factors (I kappa B kinase subunits and bcl-3) are implicated in hematological and solid tumour malignancies. NF-kappa B appears to be involved in cell proliferation control, apoptosis control, angiogenesis promotion and possibly regulation of diffusion of metastases. There are several reports that inhibition of NF-kappa B as a therapeutic target may have a role in tumour cell death or growth inhibition. Area covered in this review: We review data about inhibition of NF-kappa B in acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS). We describe the molecular mechanisms underlying NF-kappa B deregulation in these haematological malignancies. What the reader will gain: Constitutive activation of NF-kappa B in the nucleus has been reported in some varieties of MDS/AML. The in vitro and in vivo results of NF-kappa B inhibition in myeloid malignancies are highlighted. Take home message: NF-kappa B selective inhibitory drugs may be useful, either as single agents or associated with conventional chemotherapy.