Yamochi T, Kitabayashi A, Hirokawa M, Miura A B, Onizuka T, Mori S, Moriyama M
Department of Pathology, Institute of Medical Science, University of Tokyo, Minato-ku, Japan.
Leukemia. 1997 May;11(5):694-700. doi: 10.1038/sj.leu.2400631.
We demonstrated in the present study that the BCL-6 transcripts were detectable not only in B cells, but also in circulating granulocytes and monocytes from normal individuals, and in human acute nonlymphocytic leukemia cells of certain subtypes (M3, M4, M5). Then, with an assumption that the BCL-6 gene expression may be related to the differentiation of myeloid cells, we analyzed the inducibility of BCL-6 gene expression along monocytic lineage differentiation in HL-60 and U-937 cells by treating them with 12-O-tetradecanoylphorbol-13-acetate (TPA). Although the expression of BCL-6 transcripts was very low or undetectable in untreated HL-60 or U-937 cells, treatment of these cells with TPA to induce monocytic differentiation resulted in an apparent increase of BCL-6 mRNA, suggesting that BCL-6 gene expression is not limited to B cells and it is closely associated with monocytic lineage differentiation. The BCL-6 transcripts in TPA-treated U-937 cells were superinduced by the treatment with cycloheximide (CHX) and the half-life of the BCL-6 mRNA was apparently prolonged when TPA-treated U-937 cells were exposed to CHX in the presence of actinomycin D (ACD). Furthermore, the nuclear run-on assay revealed that the BCL-6 transcription signals were enhanced by TPA treatment. These results suggest that the increase of BCL-6 mRNA in U-937 cells stimulated with TPA to induce monocytic lineage differentiation is mediated by both transcriptional and post-transcriptional regulation.
我们在本研究中证明，BCL-6转录本不仅在B细胞中可检测到，在正常个体的循环粒细胞和单核细胞中也可检测到，在某些亚型（M3、M4、M5）的人类急性非淋巴细胞白血病细胞中同样可检测到。然后，基于BCL-6基因表达可能与髓系细胞分化相关的假设，我们通过用12-O-十四酰佛波醇-13-乙酸酯（TPA）处理HL-60和U-937细胞，分析了BCL-6基因表达在单核细胞系分化过程中的可诱导性。尽管在未处理的HL-60或U-937细胞中，BCL-6转录本的表达非常低或无法检测到，但用TPA处理这些细胞以诱导单核细胞分化会导致BCL-6 mRNA明显增加，这表明BCL-6基因表达不仅限于B细胞，且与单核细胞系分化密切相关。用环己酰亚胺（CHX）处理TPA诱导的U-937细胞可使BCL-6转录本超诱导表达，并且当TPA处理的U-937细胞在放线菌素D（ACD）存在的情况下暴露于CHX时，BCL-6 mRNA的半衰期明显延长。此外，核转录分析显示TPA处理可增强BCL-6转录信号。这些结果表明，TPA刺激U-937细胞诱导单核细胞系分化时BCL-6 mRNA的增加是由转录和转录后调控共同介导的。
