Rearranged NF-κB2 gene in an adult T-cell leukemia cell line

Abstract

Adult T-cell leukemia (ATL) is an aggressive type of leukemia, originating from T-cells infected with human T-cell leukemia virus type 1. Accumulating evidence suggests the aberrant activation of NF-κB to be a causative factor mediating the abnormal proliferation of leukemic cells, thus resulting in the development of ATL. A rearranged NF-κB2/p100 gene was isolated from an ATL-derived cell line, which was generated by a chromosomal translocation. The isolated NF-κB2 mutant is fused with the with no (lysine) deficient protein kinase 1 gene, coding for a 58 kDa protein that retains the DNA binding Rel homology domain, but it lacks the entire ankyrin repeat inhibitory domain, thus suggesting its constitutive activation. This rearranged NF-κB2 gene product (p58) was localized in the nucleus, and formed a complex with NF-κB p65 or RelB. Moreover, a T-cell line expressing p58 increased the amount of an NF-κB2-inducible gene, NF-κB2/p100 by itself. These results suggest that such NF-κB2 gene rearrangement may therefore be a factor in the constitutive activation of NF-κB in ATL, and thereby playing a role in the ATL pathogenesis. © 2008 Japanese Cancer Association.