白血病细胞TGFβ_1及其受体基因表达与白血病患者血清TGFβ_1测定及其意义  

Study on gene expression of TGFβ_1 and its receptor in leukemia cells and the serum TGFβ_1 level in the patients with acute leukemia

作　　者：陈元仲[1] 吕联煌[1] 汪玲 彭永麟 JPCaen 韩忠朝 

机构地区：[1]福建医学院 [2]法国巴黎血管血液研究所

出　　处：《中华血液学杂志》1998年第11期576-580,共5页Chinese Journal of Hematology

基　　金：国家教委优秀青年教师基金[教人司1995(503)];福建省教委科研基金(K95033)

摘　　要：目的:研究转化生长因子β_1(TGFβ_1)对白血病细胞增殖抑制作用的机制及急性白血病患者血清TGFβ_1变化及意义。方法:应用逆转录-聚合酶链反应方法检测白血病细胞的细胞因子及其受体基因表达;应用白血病细胞集落试验测定TGFβ_1对HL-60、DAMI、K562细胞增殖的作用;应用ELISA方法测定33例急性白血病患者血清TGFβ_1水平。结果:TGFβ_1对HL-60、K562、DAMI细胞增殖具有明显的抑制作用;白血病细胞系(HEL、HL-60、K562、U937、DAMI、MEG-01、HUT78)及CA均表达TGFβ_1及其受体mRNA。外源性TGFβ_1抑制DAMI细胞IL-6、IL-6R、GM-CSFR及IL-3的基因表达,上调DAMI细胞本身TGFβ_1表达,并诱导DAMI细胞凋亡。白血病患者血清TGFβ_1水平明显减低;患者达完全缓解时,该水平恢复正常;复发时,该水平又趋减低。结论:TGFβ_1是白血病细胞抑制性自泌因子;其抑制作用与其调控白血病细胞的细胞因子与受体表达有关;血清TGFβ_1水平是监测白血病病情转归的一项有价值指标;TGFβ_1作为负调控因子在白血病发病机制中可能起重要作用。Objective: To investigate the mechanism by which TGFβ_1 inhibits the growth of leukemic cells and the significance of serum TGFβ_1 level in acute leukernia(AL) patients. Methods: RT-PCR was used to de- tect gene expression of cytokines including IL-1, IL-3, IL-6,TGFβ_1 and their receptors (R) in leukemic and normal cells. Leukemic colony assay was carried out to determine the effect of TGFβ_1 on the growth of leukemic cells and the serum TGFβ_1 level in 33 AL patients were measured by ELISA. Results: TGFβ_1 was found to sig- nificantly inhibit the proliferation of leukemia cells of HL-60, K562 and DAMI cell lines. Furthermore, a variety of leukemia cell lines including HEL, HL-60, K562, U937, DAMI, MEG-01, HUT78 and CA were found to express mRNAs for TGFβ_1 and its receptor. In addition, TGFβ_1 was found to be able to evidently down-regu- late the expression of mRNAs for IL-6, IL-6R, IL-3, GM-CSFR in DAMI cells and, interestingly, up-regulate TGFβ_1 gene expression in the cells per se before the cells showed DNA fragmentation, a molecular hallmark for cell apoptosis. It was shown that serum TGFβ_1 levels were significantly decreased in leukanic patients, restored to normal in the patients achieved complete remission, and tended to decrease again in the recurrent patients. Conclusion: ①TGFβ_1 may act as an inhibitory autocrine factor in the proliferation of leukemia cells; ②the mechanism by which TGFβ_1 inhibits the growth of leukemia cells involves its down-regulating expression of pos- itive cytokines and receptors and up-regulating TGFβ_1 expression in leukemia cells per se; ③serum TGFβ_1 is a valuable parameter in monitoring the prognosis of leukemia and weakened control of TGFβ_1 on leukemia cells may play an important role in the pathogenesis of AL.

关 键 词：转化生长因子Β 白血病 细胞凋亡 基因表达 

分 类 号：R733.7[医药卫生—肿瘤]