白血病细胞对白细胞介素-2的反应研究

为研究重组人ＩＬ－２（ｒｈＩＬ－２）对白血病治疗的可用性和安全性，用３Ｈ胸腺嘧核苷（３ＨＴｄＲ）掺入法检测有白介素－２受体（ＩＬ－２Ｒ）基因表达的７个白血病细胞株，６例急性淋巴细胞白血病（ＡＬＬ）患者和８例急性髓细胞白血病（ＡＭＬ）患者白血病细胞体外对ｒｈＩＬ－２的反应性。结果显示：ＩＬ－２Ｒ基因表达阳性细胞体外对ｒｈＩＬ－２的反应呈不均一性。ＩＬ－２ＲαｍＲＮＡ和ＩＬ－２ＲβｍＲＮＡ均为阳性的Ｎｕｌ细胞株ＮＫＬ－１，２例ＡＬＬ和１例Ｍ５型ＡＭＬ患者细胞呈增殖反应；３个白血病细胞株，２例ＡＬＬ和２例ＡＭＬ患者细胞呈抑制反应，其余３个白血病细胞株及７例患者白血病细胞对ｒｈＩＬ－２无反应。本研究表明：白血病细胞对ｒｈＩＬ－２的反应不均一，可出现增殖、受抑或不反应。给白血病细胞体外对ｒｈＩＬ２呈受抑和无反应的患者使用ｒｈＩＬ－２作免疫治疗是合适的，而白血病细胞呈增殖反应者不宜使用ｒｈＩＬ－２。     

急性髓细胞白血病细胞IL-2受体基因的研究

为研究髓细胞白血病（ＡＭＬ）细胞白介素－２受体（ＩＬ－２Ｒ）基因及ＩＬ－２在ＡＭＬ中的作用，用逆转录－聚合酶链反应（ＲＴ－ＰＣＲ）对４１例ＡＭＬ患者化疗前白血病细胞ＩＬ－２ＲαｍＲＮＡ和ＩＬ－２ＲβｍＲＮＡ进行检测，并对部分ＩＬ－２Ｒ基因阳性表达细胞用３Ｈ－ＴｄＲ掺入法测定其对重组人ＩＬ－２（ｒｈＩＬ－２）的反应。结果显示，ＡＭＬ细胞ＩＬ－２Ｒα和ＩＬ－２β基因表达是一普遍现象，４１例中白血病细胞有ＩＬ－２ＲαｍＲＮＡ和ＩＬ－２ＲβｍＲＮＡ表达分别为２８例（６８．３％）和３２例（７８．０％），ＩＬ－２ＲαｍＲＮＡ和ＩＬ－２ＲβｍＲＮＡ同时表达者２１例（５１．２％）。ＩＬ－２Ｒ基因阳性表达细胞对ｒｈＩＬ－２的体外反应呈不均一性，表现为细胞增殖、受抑或不反应，８例中仅１例Ｍ５型患者细胞呈增殖反应。本研究表明ＡＭＬ细胞ＩＬ－２Ｒ基因表达是一普遍现象，这些细胞在体外对ｒｈＩＬ－２的反应呈不均一性，大多表现为无反应或受抑。     

急性髓细胞白血病细胞IL—2受体基因的研究

为研究髓细胞白血病（ＡＭＬ）细胞白介素－２受体（ＩＬ－２Ｒ）基因及ＩＬ－２在ＡＭＬ中的作用，用逆转录－聚合酶链反应（ＲＴ－ＰＣＲ）对４１例ＡＭＬ患者化疗前白血病细胞ＩＬ－２Ｒα ｍＲＮＡ和ＩＬ－２ＲβｍＲＮＡ进行检测，并对部分ＩＬ－２Ｒ基因阳性表达细胞用＾３Ｈ－ＴｄＲ掺入法测定其对重组人ＩＬ－２（ｒＨＩＬ－２）的反应。结果显示，ＡＭＬ组织ＩＬ－２Ｒα和ＩＬ－２β基因表达是一普遍现象，４１例中白血病     

重组人白细胞介素6对人肺癌细胞系生长的调控及机制研究

探讨重组人白细胞介素６（ＩＬ－６）对人肺癌生长调控作用及机制。方法以人肺巨细胞癌系ＰＧ和人肺腺癌细胞系ＰＡａ为研究对象，研究ｒｈＩＬ－６对ＰＧ、ＰＡａ细胞体外生长的作用；并应用Ｎｏｒｔｈｅｒｎ杂交检测ｒｈＩＬ－６对ＩＬ－６、ＩＬ－６受体（ＩＬ－６Ｒ）、ｃ－ｍｙｃ、ｃ－ｆｏｓ、ｃ－ｊｕｎ等基因表达的影响。结果发现ｒｈＩＬ－６促进ＰＧ、ＰＡａ细胞生长，呈浓度依赖性和时间依赖性。逆转录聚合酶链反应检测证实，ＰＧ、ＰＡａ细胞均表达ＩＬ－６及ＩＬ－６ＲｍＲＮＡ。ｒｈＩＬ－６上调ＩＬ－６、ＩＬ－６Ｒ及ｃ－ｍｙｃ等基因表达，而对ｃ－ｆｏｓ、ｃ－ｊｕｎ基因表达无明显影响。结论ｒｈＩＬ－６促进ＰＧ、ＰＡａ细胞生长；ｒｈＩＬ－６上调ＩＬ－６、ＩＬ－６Ｒ及ｃ－ｍｙｃ等基因表达作用可能与其促进ＰＧ、ＰＡａ细胞生长有关     

白血病患者血T淋巴细胞亚群和sIL-2R水平的变化

目的：探讨白血病患者外周血Ｔ淋巴细胞亚群和可溶性白细胞介素－２受体（ｓＩＬ－２Ｒ）的变化。方法：分别应用单克隆抗体技术和酶联吸附试验检测３１例白血病患者外周血Ｔ淋巴细胞亚群和ｓＩＬ－２Ｒ水平,并以３５名正常人作对照。结果：白血病患者外周血ＣＤ３＾＋、ＣＤ４＾＋细胞数低于正常人,ＣＤ８＾＋细胞数高于正常人（Ｐ〈０．０１）,ＣＤ４＾＋／ＣＤ８＾＋比值下降（Ｐ〈０．０１）。血清ｓＩＬ－２Ｒ活性明显高于正     

慢性乙肝患者sIL—2R和T细胞亚群检测

该文对２３例慢性乙型肝炎患者应用单抗夹心ＬＬＩＳＡ法检测血清ｓＩＬ－２Ｒ，ＡＰＡＡＰ桥联法检测外周血Ｔ淋巴细胞亚群，结果显示慢性乙型肝炎患者血清ｓＩＬ－２Ｒ水平显著高于正常组（Ｐ〈０．０１），Ｔ淋巴细胞亚群与正常组比较，ＣＤ４＾＋、ＣＤ３＾＋细胞显著降低，ＣＤ＾８＋比值显著降低（Ｐ〈０．０１），且血清ｓＩＬ－２Ｒ水平与患者血清谷丙转氨酶、ＨＢｅＡｇ关系密切。表明慢性乙型肝炎患者血清ｓＩＬ－２Ｒ水平     

急性白血病患者血清白细胞介素—2及T淋巴细胞亚群水平测定

目的：探讨急性白血病（ＡＬ）患者血清白细胞介素－２（ＩＬ－２）及血液Ｔ细胞亚群水平。方法：采用酶联免疫吸附试验（ＥＬＩＳＡ）及荧光免疫法测定３０例急性白血病（ＡＬ）患者血清白细胞介素－２（ＩＬ－２）及血液Ｔ细胞亚群水平,并与对照组进行比较。结果：ＡＬ患者血清ＩＬ－２含量显著低于对照组（Ｐ〈０．０１）,Ｔ细胞亚群中ＣＤ＾＋３,ＣＤ＾＋４均低于对照组水平（Ｐ〈０．０１）,ＣＤ＾＋８高于对照组水平（Ｐ〉     

rhIL－3增强急性髓性白血病细胞体外对阿糖胞苷敏感性的研究

利用基因重组人白细胞介素３（ｒｈＩＬ－３）研究了１３例急性髓性白血病（ＡＭＬ）细胞体外对阿糖胞苷（Ａｒａ－Ｃ）的敏感性。结果，Ａｒａ－Ｃ对ＡＭＬ细胞的杀伤在不同的病例之间差异较大；在ｒｈＩＬ－３存在下，Ａｒａ－Ｃ对ＡＭＬ细胞的杀伤明显增强（Ｐ＜０．００１）。ＡＭＬ细胞对ｒｈＩＬ－３的反应具有异质性。探讨了ｒｈＩＬ－３与化疗药物联合用于治疗ＡＭＬ的可能性。     

白血病患者血清可溶性白细胞介素-2受体的检测

目的：检测白血病患者血清可溶性白细胞介素－２受体（ＳＩＬ－２Ｒ）水平、缓解期ＣＤ４、ＣＤ８及慢笥粒细胞白血病（ＣＭＬ）患者ｐｈ＾１染色体阳性率以按摩ＳＩＬ－２Ｒ水平变化的临床意义及其与ＣＤ４、ＣＤ８及ｐｈ＾１阳性率的关系。方法：双抗体夹心酶联免疫吸附法测ＳＩＬ－２Ｒ,ＡＰＡＡＰ法测ＣＤ４－ＣＤ８阳性率;Ｒ显带法测ＣＭＬ的ｈｐ＾１阳性率。结果：白血病组ＳＩＬ－２Ｒ水平高于对照组（Ｐ均〈０．０１）,且     

白细胞介素—Ⅱ和LAK细胞对放疗后鼻咽癌患者细胞免疫功能的影响

目的 探讨白细胞介素－Ⅱ（ＩＬ－２）和ＬＡＫ细胞对鼻咽癌（ＮＰＣ）放疗后患者免疫功能的影响。方法 ２７例放疗后获ＣＲ的患者分成２组;Ａ组（治疗组）,１７例接受ＣＲ的患者分成２组;Ａ组（治疗组）,１７例接受ＩＬ－２和ＬＡＫ细胞治疗;Ｂ组（对照组）,１０例仅予一般治疗。检测两组治疗前后ＮＫ活性和ＣＤ４＾＋／ＣＤ８＾＋比值均明显提高（Ｐ〈０．０５）,Ｂ组则无明显变化。结论 ＩＬ－２和ＬＡＫ细胞治疗可增加     

Bone marrow Th2 cytokine expression as predictor for relapse in childhood acute lymphoblastic leukemia (ALL)

The immunological environment of leukemic blasts in the bone marrow might play a decisive role in determining an individual's risk for relapse. In order to identify potential predictors of relapse and to elucidate the mechanisms of immune control of leukemic blasts we examined the expression of cytokines, costimulatory molecules and members of the TNF family in leukemic marrow samples in a prospective study. Samples from 49 consecutive pediatric patients with B cell precursor acute lymphocytic leukemia (BCP ALL) were analyzed by semiquantitative RT-PCR. We identified interleukin (IL)-10 expression as a significant adverse prognostic indicator in childhood BCP-ALL. The event free survival (EFS) of patients expressing IL-10 mRNA in high quantity was significantly lower compared with patients expressing low IL-10 mRNA. Taqman RT-PCR of sorted cell populations showed that IL-10 mRNA was synthetized almost exclusively by NK or T cells. In addition, we found an increased expression of IL-1, IL-4, CD86 and VEGF mRNA in patients with late relapses. Possibly, ALL cells mediate a Th2 shift through increased expression of CD86 and thereby influence the individual relapse risk. These findings emphasize the role of the immune system for the outcome of childhood ALL.     

增殖细胞核抗原、ras癌基因产物P21与白血病的相关性

目的探讨急性白血病及骨髓增生异常综合征（MDS）患者增殖细胞核抗原（PCNA）、ras-P21表达的相关性及其临床意义。方法采用单克隆抗体免疫细胞化学染色技术（SP法）检测33例急性髓细胞白血病（AML）、18例急性淋巴细胞白血病（ALL）、25例MDS及10例正常人的增殖细胞核抗原（PCNA）及ras-P21的表达，分析其相关性。结果AML、ALL及MDS PCNA的阳性率分别为62％，56％和53％，三者阳性率差别无统计学意义（P〉0．05）。AML与ALL、AML与MDS的PCNA表达强度（阳性细胞％）差别无统计学意义（X^2值分别为2．027和0．5217）。2例半年内转化成AML的MDS患者为PCNA高表达。17例ras-P21阳性者均有PCNA表达。结论ras-P21和PCNA共同表达的白血病细胞增殖活性及恶性增殖的潜能更高，ras-P21和PCNA综合检测对于白血病细胞增殖活性和预后分析可能具有参考价值。     

Acute leukemia in adults: assessment of remission induction with combination chemotherapy by clinical and cell-culture criteria.

Remission induction was assessed by clinical and cell-culture criteria for 65 patients with acute myelogenous leukemia (AML), 11 patients with chronic myelogenous leukemia (CML) in blast crisis and 19 patients with acute lymphoblastic leukemia (ALL). Cyclophosphamide, cytosine arabinoside and vincristine (CAV) therapy resulted in complete remission in 23 of 50 previously untreated patients with AML and in 3 of the 11 patients with CML. Fourteen patients with ALL responded to vincristine-prednisone induction therapy and two to induction therapy with CAV. The median duration of survival of the responding patients was 2.2 years, compared with 4 months for the patients who did not respond to treatment. Granulopoietic colony formation, assessed by assay of colony-forming units dependent on colony-stimulating activity in culture (CFU-C), was abnormal in 37 of 42 bone marrow aspirates from patients with AML before treatement. CFU-C concentration increased when leukocyte-conditioned medium (LCM) was added to the cultures; 13 cultures had normal or elevated CFU-C concentration with LCM. Marrow cells of patients with ALL or CML in blast crisis demonstrated a similar pattern. Serial studies of marrow CFU-C concentration of 31 patients with AML demonstrated a change to a normal pattern with successful remission induction. Results of this study suggest that administration of purified LCM to leukemic patients might increase granulocyte production from potential but unstimulated granulopoietic precursors. This therapy would lessen the probability of death from infection during remission induction.     

Expressions of IL-10 on leukemic cells in acute leukemic patients and its significance

Objective: To explore the expressions of IL-10 on leukemic cells in acute leukemia patients and its significance.Methods :The expressions of IL-10 on leukemic cells in thirty patients was measured by indirect immunofluorescence technique. Results:Observed yellow-green bright fluorescence on leukemic cells membrane, the positive rote of cells was 10-80%, there were 18 patients expressing IL-10 (18/30, 60% ) positively, among them 11 with ANLL (11/19, 58% ) and 7 with ALL (7/11, 64% ) respectively while that of peripheral mononucleate cells in control group was 13%. Compared with that in the control group, there was a significant increase of positive rote in ANLL and ALL but with no significant difference between ANLL and ALL. Conclusion: IL-10 secreted by leukemic cells, contributed to the immunosuppressive state at the tumor site. This is probably one of the important mechanisms of acute leukemic escape.     

急性髓系白血病免疫治疗方式及研究进展

急性髓系白血病(AML)是不成熟的造血细胞在骨髓内聚集、不断扩增并抑制造血的一类疾病,其核心治疗方案近30年基本保持不变,但疾病的预后及生存率仍不理想。然而,目前针对机体免疫机制的研究使得免疫治疗得到不断完善,因此免疫治疗可能成为今后治疗AML的有效方案,为该病的预后及生存率提供了新的武器。免疫治疗的执行方案包括:异基因造血干细胞移植、靶向治疗(基因工程T细胞、单克隆抗体等)等多种途径,通过不同机制杀伤肿瘤细胞。异基因造血干细胞移植作为AML最有效的治疗,通过免疫介导的移植物抗白血病效应根除白血病细胞,能有效预防AML复发。移植技术和单倍体移植模式进展使得“人人都能进行造血干细胞移植”。靶向治疗,如基因工程T细胞(嵌合抗原受体T细胞)、单克隆抗体、新型双特异性单抗,能特异性杀伤表达特殊抗原的白血病细胞而不伤害正常细胞,将成为AML免疫治疗的新策略。其他如自然杀伤细胞,结合NK细胞治疗可安全、有效降低AML复发风险,此外,增强NK细胞活性可能是今后最佳的白血病治疗方案。虽然现在仍然有部分方案尚处于研究阶段,但免疫治疗将成为今后治疗AML的重要手段。本文将对目前AML免疫治疗的研究进展及相关分子学机制进行综述。      

The effects of IL-10 on acute leukemic immune evasion

Objective：To explore the effects of IL-10 on acute leukemic immune evasion. Methods： Plasma concentrations of IL-10 were measured by ELISA in 56 first-visit acute leukemic patients. And expressions of IL-10 on leukemic cells in 30 patients were measured by indirect immunofluorescence technique.Results： Compared with those in control group,IL-10 concentrations increased significantly in first-visit acute leukemic patients. And there was a slight but not significant decrease of IL-10 in patients with acute lymphocytic leukemia(ALL) compared with those with acute non lymphocytic leukemic(ANLL). After intensive chemotherapy,there was a significant decrease of IL-10 in completely remitted (CR) patients ,especially in those with ANLL,but there was still a significant increase compared with those in control group.The positive rate of cells giving out yellow-green bright fluorescence on membranes was 10%-80% ;there were 18 patients expressing IL-10(18/30,60%) positively:among them 11 with ANLL(11/19,58%) and 7 with ALL(7/11,64 %) respectively while that of peripheral mononucleate cells in control group was 13%.Compared with that in control group,there was a significant increase of positive rate in ANLL and ALL but with no significant difference between ANLL and ALL. Conclusion： Probably as one of important mechanisms of acute leukemic immune evasion,IL-10 secreted by leukemic cells,contributing to the immunosuppressive state at the tumor site ,increase significantly in acute leukemic patients.     

小儿急性白血病的免疫表型研究及电镜观察

应用系列单克隆抗体对29例小儿急性白血病进行免疫表型研究,并对其中的12例作电镜超微结构、电镜细胞化学观察。结果显示,用不同研究手段对白血病进行髓系、淋系的分类诊断基本(?)符,根据白血病细胞免疫表型可以明确细胞的不同来源及分化程度,研究中还发现,有较多的混合表型病例(24%)。提示白血病细胞常表现为异质性抗原表达紊乱。电镜观察可以弥补光镜的不足,与光镜结合可提高诊断水平。     

白细胞介素3受体α亚基与急性髓系白血病的靶向治疗

目前的化疗方案可能已达到治疗急性髓细胞白血病(AML)的极限,今后急性髓系白血病治疗的探索方向更多地是转向靶向治疗。单克隆抗体治疗已经在复发AML中产生明显的缓解率。在AML越来越多的异常分子描述中,白细胞介素3受体(IL-3R)α值得高度关注。IL-3R是造血生长因子受体家族成员之一,其α亚基CD123是白血病干细胞的特异标志,在白血病的发生和白血病细胞增殖、分化及凋亡中发挥重要作用。绝大部分急性髓系白血病高表达IL-3Rα。针对IL-3Rα靶向治疗的Ⅰ期临床研究已显示出一定的疗效。