Normal Structure of NFKB 2, C-REL and BCL-3 Gene Loci in Lymphoproliferative and Myeloproliferative Disorders

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Abstract
NF-kappaB/rel transcription factors are crucial regulators of development, differentiation and apoptosis of both lymphoid and myeloid lineages. There is increasing evidence for an involvement of NF-kappaB/rel proteins in lymphomagenesis and resistance of lymphoid tumors to the induction of apoptosis. Structural alterations of the NF-kappaB/rel genes NFkappaB2, c-rel and bcl-3 have been shown to result in increased NF-kappaB/rel activity. Because we observed strong constitutive NF-kappaB/rel binding activity in chronic lymphocytic leukemia of the B-cell type (B-CLL) which may contribute to resistance against cytotoxic drugs we studied the genomic organisation of NFkappaB2, c-rel and bcl-3 gene loci in a panel of lymphoproliferative disorders (n=81) with an emphasis on B-CLL (n=47). The method of genomic Southern blotting using cDNAs of the respective genes was used. In spite of the role of NF-kappaB/rel in myeloid maturation there is no data available as to the occurrence of NF-kappaB/rel rearrangements in chronic myeloproliferative syndromes (cMPS). For this reason we included a small panel of cMPS patients (n=16). Southern Blotting revealed a germline configuration of NFkappaB2, c-rel and bcl-3 loci in all NHL and cMPS patients examined. Our results demonstrate that structural alterations of NFkappaB2, c-rel and bcl-3 genes at the Southern Blotting level are rare events that do not contribute to lymphoid or myeloid transformation in the majority of NHL or cMPS patients.