微波在白血病无损探测中的应用—数值结果

本文讨论应用微波对白血病进行无损探测的可能性。在建立柱坐标系下分析人体小腿微波散射特性的时域有限差分算法模型的基础上，具体计算了三种不同微波频率下人体小腿上部的微波散射特性及白血病的存在对其产生的影响。数值结果表明，当存在白血病时人体小腿上部的微波散射特性有较大变化，据此可以判断白血病存在及其病变程度。该技术可应用于白血病的无损探测及治疗过程中的监测。     

Induction of apoptosis and CD10/neutral endopeptidase expression by jaspamide in HL-60 line cells

Jaspamide (jasplakinolide) is a natural peptide isolated from marine sponges of Jaspis species and has fungicidal and growth-inhibiting activities. We characterized the jasplakinolide-induced loss of viability by programmed cell death in the HL-60 human promyelocytic leukemia cell line and found that this process was accompanied by neutral endopeptidase (NEP)/CD10 expression on the surface of the apoptotic cells. HL-60 cells do not normally express detectable amounts of NEP/CD10 on their surface or intracytoplasmically, but upon jaspamide treatment, CD10 was synthesized de novo, its expression being inhibited by cycloheximide pretreatment. Once synthesized, NEP/CD10 interfered with the jasplakinolide signal delivered to HL-60 cells. Inhibition of NEP/CD10 by the NEP inhibitor phosphoramidon or by an anti-CD10 monoclonal antibody significantly increased apoptosis induction. The appearance of CD10 on the cell surface was blocked by preincubation of the cells with the monocytic/macrophage-differentiating agents vitamin D3 and phorbol 12-myristate 13-acetate, but not by the granulocytic differentiating agents retinoic acid or dimethyl sulfoxide. Moreover, in the promonocytic U937 and mature monocytic THP-1 cell lines, jaspamide induced apoptosis but not CD10 expression. In HL-60 cells, CD10 expression was partially but not totally blocked by the broad-spectrum caspase inhibitor benzyloxacarbonyl-Val-Ala-Asp-fluoromethylketone, indicating a connection between apoptosis induction and CD10 synthesis. Our findings suggest that the CD10 expression is related to the programmed cell death induction by jaspamide, and also with the process of granulocytic differentiation in HL-60 cells. Received 22 April 2002; received after revision 8 June 2002; accepted 10 June 2002     

急性白血病T淋巴细胞及其亚群的研究

应用McAb检测31例急性白血病患者外周血T细胞及其亚群的改变。结果表明总T细胞(T_1)、T辅助细胞(T_4)和T抑制细胞(T_8)百分率均明显低于正常对照组(P<0.01～0.001),且伴有T_4:T_8值的下降(P<0.05)。经化疗缓解后,部分缓解组T细胞及其亚群均恢复正常,完全缓解组T_4细胞仍稍低于正常值(P<0.05)。化疗无效组T细胞及其亚群的改变与未治疗组类似(P>0.05)。急淋T-ALL型时,外周血T细胞及其亚群的改变与一般白血病表现不同,其T细胞标记及T_4:T_8值反而增高。病情缓解时逐渐恢复正常急淋其它型患者,其T细胞及亚群的改变与急非淋患者类似。结果提示,动态观察T细胞及其亚群变化,有助于对白血病患者疗效及预后的判定。     

双色荧光定量PCR检测慢性粒细胞白血病(CML)患者BCR/ABL融合基因的表达

根据常见的BCR/ABL融合基因序列,分别设计合成检测BCR/ABL融合基因和ABL基因表达的TaqMan引物、探针,其中检测融合基因表达的探针标记FAM荧光素,检测ABL基因表达的探针标记HEX荧光素,检测BCR/ABL融合基因探针标记FAM荧光素的;提取患者骨髓细胞标本总RNA,逆转录成cDNA;以其为模板在同一PCR扩增管中同时进行两种基因的双色荧光定量PCR反应,分别定量测定BCR/ABL融合基因和ABL基因的表达量,并计算两种基因表达的比值;采用该基因检测技术检测20例CML患者BCR/ABL融合基因及ABL基因的表达量,与临床诊断结果对比,判断该技术在CML检测诊断中的价值.成功地建立了双色荧光定量PCR技术方法,在20例患者中检出18例融合基因阳性,检测阳性率90％.     

T—ALL／淋巴瘤中BCL11B基因转录本的分析

目的:分析T-ALL/淋巴瘤中BCL11B基因转录本的特点。方法:利用逆转录聚合酶链式反应(RT-PCR)和实时定量聚合酶链式反应(RQ-PCR)方法分析12例T-ALL/淋巴瘤外周血单个核细胞(PBMC)中BCL11B基因的表达情况;限制性内切酶消化确定PCR产物的特异性。结果:3例T-ALL/淋巴瘤患者中出现2种BCL11B转录本:野生型和第3外显子缺失型,其余9例均表达第3外显子缺失型的转录本。两组病人PBMC中BCL11B表达水平无显著差别(P=0.301)。结论:3例T-ALL/淋巴瘤病人中存在2种BCL11B基因转录本,但在表达水平上无明显差别。     

重组人促红细胞生成素对K562/A02多药耐药和K562药物敏感细胞增殖的影响

用ＭＴＴ法测定了重组人促红细胞生成素（ｒｈｕ－ＥＰＯ）对Ｋ５６２／Ａ０２多药耐药细胞系细胞和Ｋ５６２药物敏感细胞增殖的影响。研究发现,Ｋ５６２／Ａ０２与浓度为００７８、０１５６Ｕ／ｍＬ的促红素分别孵育时,其增殖活力比无ｒｈｕ－ＥＰＯ因子组低（Ｐ＜００１）;而Ｋ５６２与上述同样浓度的ｒｈｕ－ＥＰＯ孵育条件下,其增殖活力与无因子组比较差异无显著性意义（Ｐ＞０２０）。以上结果表明,ｒｈｕ－ＥＰＯ可能有抑制Ｋ５６２／Ａ０２细胞增殖的作用,而对Ｋ５６２细胞增殖无影响,提示ｒｈｕ－ＥＰＯ可能对多药耐药白血病的治疗有一些效果     

重建人类免疫系统的人源化小鼠模型及其在血液系统疾病研究中的应用

动物模型在人类疾病发病机制的研究及药理学实验研究治疗中发挥重要作用。小鼠是目前主要的实验动物,但其与人类背景存在差异,不能完全模拟人类免疫系统及疾病状态。研究人员通过将人类细胞或组织植入免疫缺陷小鼠体内,可构建免疫系统人源化小鼠模型及人源化小鼠疾病模型。人源化小鼠可通过优化人源造血干细胞来源等条件,可得到免疫系统人源化程度较高的小鼠模型。目前,GVHD人源化小鼠模型及白血病人源化小鼠模型已经应用在研究疾病发病机制及开发新型临床治疗药物等方面。     

非妊娠小鼠子宫内膜白血病抑制因子基因表达研究

白血病抑制因子（LIF）能抑制胚胎干细胞的分化和保持其增殖能力,并与胚泡着床及胚胎早期发育有着密切的关系。经实验证实,LIF基因在子宫内膜中的表达具有高度的时间限制性。采用反转录聚合酶链式反应技术（RT－RCR）对小鼠子宫内膜LIF基因表达进行了研究,结果显示：妊娠第4天小鼠的子宫内膜组织的样本在电泳图的538bp处出现清晰的电泳带,表明该组织有LIF基因的强表达;而在所检测的13只非妊娠小鼠子宫内膜的组织样本中均未发现LIF基因表达讨论了小鼠动情周期中各阶段的孕激素水平对子宫内膜LIF基因表达产生的影响,提出了一定的孕激素水平是启动LIF基因表达的必要条件     

白血病发病原理研究：“多次打击”学说

白血病是一种基因组发生动态变化的造血干/祖细胞疾病,染色体易位和/或基因突变是常见的遗传学异常。近来,研究提示白血病的发生多遵循“多次打击”模式。在慢性粒细胞白血病中,GATA-2突变可能与BCR-ABL共同作用导致“急变”;在M2b型急性髓性白血病中,C-KIT突变可能是在AML-ETO基础上的再次遗传学异常;在TEL-AML1相关的儿童急性淋病细胞白血病中,正常TEL基因丢失作为第二次打击而致病。作者以上述三种白血病为例,阐述其发病原理以及靶向治疗研究所取得的进展。     

The study on BCR/ABL fusion gene in adult acute lymphoblastic leukemia

In order to assess the significance of BCR/ABC fusion gene in adult acute lymphoblastic Leukemia (ALL), 28 patients who were diagnosed as ALL were enrolled to detect BCR/ABC gene using nested-RT-PCR. The results showed that 9 cases (31.25%) were BCR/ABL positive, and expressed P210 subtype. Among them 7 cases were B-ALL, and one was T-ALL. The diagnosis was proved by monoclonal antibodies recognition by indirect immunofluorescence. Adult patients with BCR/ABL positive ALL were significantly older (p<0.01) and had higher WBC count (p<0.01) as compared with BCR/ABL-negative patients. There was no significant difference in sex, hemoglobin and splenomegaly between two group (p>0.05). The induction failure rate was high in BCR/ABL positive patients and those who achieved complete remission usually relapsed earlier. In conclusion, adult ALL patients with BCR/ABL-positive have poorer prognosis. Biography: Li Hui-yu(1960-), female, M.S., research direction: hematology melucular