Normal structure of NPKB2, C-REL and BCL-3 gene loci in lymphoproliferative and myeloproliferative disorders
Normal structure of NPKB2, C-REL and BCL-3 gene loci in lymphoproliferative and myeloproliferative disorders
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DOI：
10.3109/10428190009087031
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发表时间：
2000-07-01
影响因子：
2.6
通讯作者：
Bergmann, L
中科院分区：
文献类型：
--
作者：
Munzert, G;Kreitmeier, S;Bergmann, L
核因子-kappaB/Rel转录因子是淋巴系和髓系细胞发育、分化和凋亡的重要调节因子。越来越多的证据表明，核因子-kappaB/Rel蛋白参与了淋巴肿瘤的发生和对诱导细胞凋亡的抵抗。核因子-kappaB/Rel基因NFKB2、c-Rel和bcl3的结构改变导致核因子-kappa B/Rel活性增加。由于我们在B细胞型慢性淋巴细胞白血病(B-CLL)中观察到了很强的结构性核因子-kappaB/Rel结合活性，这可能与对细胞毒药物的耐药性有关，所以我们研究了一组淋巴增生性疾病(n=81)中NFKB2、c-Rel和bcl-3基因座的基因组组织，重点是B-CLL(n=47)。采用基因组Southern杂交的方法，利用各自基因的cDNA。尽管核因子-kappaB/Rel在髓系成熟过程中起着重要作用，但在慢性骨髓增殖性综合征(CMPS)中核因子-kappaB/Rel重排的发生尚无相关数据。出于这个原因，我们纳入了一组中医患者(n=16)。Southern杂交显示NFKB2、c-Rel和bcl3基因座在所有受检的NHL和CMPS患者中均为胚系结构。我们的结果表明，在大多数NHL或CMPS患者中，在Southern blotting水平上NFKB2、c-Rel和BCL-3基因的结构变化是罕见的，不会导致淋巴或髓系转化。
NF-kappa B/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-kappa B/rel proteins in lymphomagenesis and resistance of lymphoid tumors to the induction of apoptosis. Structural alterations of the NF-kappa B/rel genes NFKB2, c-rel and bcl-3 have been shown to result in increased NF-kappa B/rel activity. Because we observed strong constitutive NF-kappa B/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 NFKB2, 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-kappa B/rel in myeloid maturation there is no data available as to the occurrence of NF-kappa B/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 NFKB2, c-rel and bcl-3 loci in all NHL and cMPS patients examined. Our results demonstrate that structural alterations of NFKB2, 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.