Study for the mechanism of lymphocyte development by NF-E2 transcription factors and clinical analysis of NF-E2 gene.

转录因子Bach 1和Bach 2是BTB-碱性区亮氨酸拉链（bZip）因子家族的成员，通过与Maf相关转录因子形成同源二聚体或异源二聚体，与12-O-十四烷酰基佛波醇-13-乙酸酯（TPA）响应元件和相关Maf识别元件（MARE）结合。在人造血细胞系（12种骨髓细胞系和16种淋巴细胞系）中，BACH 2仅在一些B淋巴细胞系中大量表达。造血细胞的RT-PCR分析显示BACH2 mRNA在原代B细胞中表达。在不表达内源性BACH2的人Burkitt细胞系RAJI中BACH2的强制表达导致克隆形成活性显著降低，表明BACH2对细胞增殖具有抑制作用。通过荧光原位杂交，BACH 2基因定位于染色体6q15。由于6号染色体长臂（6q）缺失是人类B细胞淋巴瘤中最常见的染色体变异之一，我们检测了人类B细胞非霍奇金淋巴瘤（NHL）中BACH 2基因的杂合性缺失（洛）。在25例有信息的病例中，5例（20%）出现洛缺失。为了分析BACH 2基因在这些淋巴瘤中的突变，我们检测了BACH 2基因的结构，并确定了所有编码外显子的序列和外显子-内含子边界。直接序列分析结果显示，5例BACH 2基因洛缺失的淋巴瘤组织均未发现突变。这些结果表明BACH 2在调节B细胞增殖中起重要作用，尽管BACH 2功能的丧失是否涉及B细胞肿瘤发生仍然是未知的。

The transcription factors Bach1 and Bach2, members of the BTB-basic region leucine zipper (bZip) factor family, bind to a 12-O-tetradecanoylphorbol-13-acetate (TPA)-responsive element and the related Maf-recognition element (MARE) by forming homodimers or heterodimers with Maf-related transcription factors. Among human hematopoietic cell lines (12 myeloid cell lines and 16 lymphocytic cell lines), BACH2 is expressed abundantly only in some B-lymphocytic cell lines. RT-PCR analysis of hematopoietic cells revealed that BACH2 mRNA is expressed in primary B-cells. Enforced expression of BACH2 in a human Burkitt cell line, RAJI that does not express endogenous BACH2, resulted in marked reduction of clonogenic activity, indicating that BACH2 possesses an inhibitory effect on cell proliferation. By fluorescent in situ hybridization, the BACH2 gene was localized to chromosome 6q15. Because deletion of the long arm of chromosome 6 (6q) is one of the commonest chromosomal alterations in human B-cell lymphoma, we examined for the loss of heterozygosity (LOH) of the BACH2 gene in human B-cell non-Hodgkin's lymphomas (NHL). Among 25 informative cases, 5 (20%) showed LOH. To analyze the mutations of BACH2 gene in these lymphomas, we examine the structure of the BACH2 gene and determined the sequences of the all coding exons and the exon-intron boundaries. By direct sequence analysis, no mutations were detected in the 5 lymphoma samples with the LOH of BACH2 gene . These results indicate that BACH2 plays important roles in regulation of B cell proliferation, although it remains still elusive whether loss of BACH2 function is involved in B-cell tumorigenesis.