title: Normal structure of NFKB2, C-REL and BCL-3 gene loci in lymphoproliferative and myeloproliferative disorders.
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.
authors.affiliation: Abteilung Innere Medizin III, Universität Ulm, Germany. gerd.munzert@medizin.uni-ulm.de
authors.forename: G
authors.initials: G
authors.lastname: Munzert
authors.forename: S
authors.initials: S
authors.lastname: Kreitmeier
authors.forename: L
authors.initials: L
authors.lastname: Bergmann
mesh_terms: D000081242:B-Cell Lymphoma 3 Protein; D015139:Blotting, Southern; D002883:Chromosomes, Human, Pair 14 / Q000235:genetics / Q000648:ultrastructure; D002888:Chromosomes, Human, Pair 19 / Q000235:genetics / Q000648:ultrastructure; D004252:DNA Mutational Analysis; D004273:DNA, Neoplasm / Q000235:genetics*; D005796:Genes; D006801:Humans; D015448:Leukemia, B-Cell / Q000235:genetics; D016393:Lymphoma, B-Cell / Q000235:genetics; D008232:Lymphoproliferative Disorders / Q000235:genetics*; D009196:Myeloproliferative Disorders / Q000235:genetics*; D016328:NF-kappa B / Q000235:genetics*; D052003:NF-kappa B p52 Subunit; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D020569:Proto-Oncogene Proteins c-rel / Q000235:genetics*; D014157:Transcription Factors; D014178:Translocation, Genetic
chemical_list: D000081242:B-Cell Lymphoma 3 Protein; C000631344:BCL3 protein, human; D004273:DNA, Neoplasm; D016328:NF-kappa B; D052003:NF-kappa B p52 Subunit; D011518:Proto-Oncogene Proteins; D020569:Proto-Oncogene Proteins c-rel; D014157:Transcription Factors