Recombinant human G-CSF and retinoic acid in synergistically inducing granulocyte differentiation of human promyelocytic leukemic cells.

The effects of recombinant human G-CSF (rhG-CSF) and retinoic acid (RA) were studied on the proliferation and differentiation of HL-60 cells and human acute myeloid leukemic cells. Synergistic effect on granulocyte differentiation was observed when HL-60 cells and primary acute promyelocytic leukemic cells were cocultured with RA plus rhG-CSF. rhG-CSF combined with RA increased more significantly the percentage of mature cells than RA alone and greatly increased NBT reduction activity (P < 0.001). These results suggested that proliferated effect of rhG-CSF on leukemic cells may be important for inducing differentiation of myeloid leukemic cells. But this effect might expose the patients to the risk of acute myeloblastic leukemia if G-CSF was used alone. However, RA could not only rule out the latter situation but retain former merit as well. The authors suggest that the combined use of G-CSF with RA is probably a new approach to the treatment of leukemia.

     

HL-60细胞分化与凋亡关系的初步研究

目的探讨HL-60细胞分化与凋亡的初步关系,指导白血病的联合化疗.方法NBT还原试验检测细胞分化、流式细胞术(FCM)检测细胞凋亡及bcl-2、c-myc蛋白的表达,观察分别经ATRA、TPA诱导分化的HL-60细胞对VP-16的凋亡反应.结果与对照组相比,经ATRA、TPA分化的HL-60细胞bcl-2、c-myc蛋白表达都明显降低(P＜0.05),其中以TPA下调c-myc蛋白的幅度最大(76%);对VP-16的诱导反应,经TPA分化的HL-60细胞凋亡率明显减少(P＜0.05),而经ATRA分化的细胞凋亡率则无明显变化(P＞0.05).结论HL-60细胞对VP-16的凋亡诱导反应与bcl-2、c-myc蛋白的下调表达程度有关;分化诱导剂ATRA与低剂量的VP-16联合应用可望改善AML的化疗效果,并且以后者先用效果更好.     

全反式维甲酸对急性白血病骨髓基质细胞JWA基因表达及粘附功能的影响

目的探讨临床患者骨髓基质细胞（BMSC）粘附功能与JWA基因表达之间的关系。方法分离培养临床急性早幼粒细胞白血病（APL）患者全反式维甲酸（ATRA）治疗前后BMSC,检测BMSC粘附能力,ICAM-1、FN表达及JWAmRNA表达变化。结果 ATRA治疗后,APL患者BMSC粘附能力、粘附分子表达及JWAmRAN表达明显增高。结论 ATRA可能通过上调JWA基因表达,促进BMSC粘附功能。     

七种癌基因在HL-60-AR细胞中的表达及药物诱导分化后的变化

用Northern杂交和斑点杂交方法分别探测HL-60-AR细胞中七种癌基因的表达及其在诱导分化后的变化。结果表明,在HL-60-AR细胞中c-myc基因高度活跃表达,H-ras基因次之,fos、sis、abl和erb-B基因表达微弱,而K-ras基因表达极微弱或检测不出。当HL-60-AR细胞被药物诱导成熟分化后,c-myc基因表达大为下降,H-ras、fos、sis、abl和erb-B基因表达亦相应降低,而K-ras的表达则无变化。对诱导分化前后c-myc基因拷贝数的比较分析表明,c-myc基因表达下降可能主要发生在基因的转录或/和转录后调节水平。     

急性早幼粒白血病细胞ATRA耐药株HL-60R、NB4R的构建及鉴定

目的：构建急性早幼粒细胞白血病细胞系HL-60、NB4的全反式维甲酸耐药株HL-60 R、NB4 R,并对其生物学性状进行鉴定。方法：以全反式维甲酸（ ATRA ）为诱导药物,采用浓度递增间歇诱导法构建HL-60、NB4细胞相应的ATRA耐药株。 CCK8法鉴定其ATRA耐药性,并检测耐药细胞株的生长曲线及多药耐药性。结果：成功构建了ATRA耐药细胞株HL-60 R、NB4 R,并发现与亲代细胞相比,其生长增殖速度减慢,群体倍增时间延长,且对其它多种化疗药物产生一定程度的交叉耐药。结论：成功构建的耐药细胞系HL-60R、NB4R为急性早幼粒细胞白血病多药耐药机制的进一步研究奠定了基础。     

白血病细胞诱导分化过程中降钙素基因异常甲基化的研究

采用ＰＣＲ检测技术，观察白血病细胞诱导分化前后ＣＴ基因甲基化型的变化和检测本方法的灵敏度及对检测白血病ＭＲＤ的意义。结果发现随着ＨＬ－６０细胞以及人早纪粒白血病体外诱导分化成熟，该基因由收藏 化状态转变为正常，２例缓解期的ＡＰＬ病人，其甲基化正常，本方法的度为１／１０００白血病细胞，如进一步提高敏感性，将有助于ＭＲＤ的检测。     

Combination of all-trans retinoic acid with butyric acid and its prodrugs markedly enhancing differentiation of human acute promyelocytic leukemia NB4 cells

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国产维甲酸治疗急性早幼粒细胞白血病疗效分析

报告全反式维甲酸分化诱导治疗17例急性早幼粒细胞白血病的疗效、缓解期与生存期、治疗期血象、骨髓象变化及维甲酸的副作用。并与常规化学治疗的14例作了比较,对比结果表明,维甲酸分化诱导治疗急性早幼粒细胞白血病完全缓解率高,服药方便,毒副作用小,治疗过程中不诱发播散性血管内凝血,也不出现骨髓抑制。全反式维甲酸应作为急性早幼粒细胞白血病诱导缓解期治疗的首选药物。     

硫化砷对急性早幼粒白血病细胞PNAS-2基因表达的影响

目的探讨硫化砷诱导急性早幼粒细胞白血病(APL)细胞凋亡的分子机制。方法应用基因表达谱芯片、RT-PCR技术，检测硫化砷作用前后NB4细胞、APL原代细胞PNAS-2基因表达的变化。结果基因表达谱芯片杂交显示，硫化砷作用于NB4细胞后，PNAS-2基因表达下调；RT-PCR结果发现，NB4细胞在硫化砷作用后PNAS-2表达有明显下调，并呈时间依赖性；APL原代细胞经硫化砷作用后，PNAS-2表达也呈下降趋势。结论硫化砷能够下调PNAS-2基因在NB4细胞株和APL原代细胞中的表达，推测PNAS-2基因可能是硫化砷治疗APL的靶基因之一。     

阿米福汀对HL-60细胞中survivin表达的影响

目的 探讨阿米福汀（WR-2721，amifostine，AMI）对人髓系白血病细胞HL-60中survivin表达的影响。方法 不同浓度AMI（1，10，1000μmol/L）干预HL-60细胞24，48，72h，用MTT比色法检测细胞的生长抑制作用;用半定量RT-PCR方法检测抑凋亡基因survivin mRNA的表达水平。结果 阿米福汀可显著抑制HL-60细胞的增殖和下调抑凋亡基因survivin的表达水平，且均有明显浓度和时间依赖性。结论 AMI可能通过下调抑凋亡基因survivin的表达，解除其抑制凋亡效应，从而抑制HL-60细胞的增殖。     

急性早幼粒细胞白血病中白血病细胞CD_(117)的表达

为观察CD117分子在急性早幼粒细胞白血病 (APL)中的表达及探讨其意义 ,采用三色流式细胞术对 2 2例APL骨髓白血病细胞表面CD117的表达进行分析。结果 :CD117在APL中的表达率为 1 9/2 2 ,在急性粒细胞白血病(AML M1)和AML M2 中的表达率分别为 2 /2和 1 8/2 1。 1 9例CD117+ 的APL患者中 ,1 8例CD34 - 、HLA DR- ,1例部分细胞HLA DR+ 。提示 :APL患者有较高水平的CD117表达 ,CD117与CD34 、HLA DR联合进行多色流式细胞术分析 ,可用于APL微小残留病灶的检测。     

维甲酸与粒—巨噬系集落刺激因子对温热诱导HL—60细胞凋亡 …

应用温和热处理诱导人急性髓系白血病细胞系ＨＬ－６０细胞发生凋亡，观察到典型的细胞形态学改变和特征性的ＤＮＡ梯型；维甲酸可促使细胞凋亡，而重组人粒－巨噬系集落刺激因子的抑制作用轻微。用斑点杂交法检测温和热处理组及维和热处理组细胞的ｃ－ｍｙｃ基因ｍＲＮＡ表达水平，二者明显低于对照组。     

Granulocyte differentiation of human promyelocytic leukemic cells induced by coordinate action of granulocyte colony stimulating factor and retinoic acid]

We analysed the effects of recombinant human G-CSF (rhG-CSF) and retinoic acid (RA) on proliferation and differentiation of HL-60 cells and human acute myeloid leukemic (AML) cells. A synergistic effect on granulocyte differentiation was observed when HL-60 cells and primary cultured acute promyelocyte leukemic cells were cocultured with 10(-8)mol/L RA plus 1:2000 or 1:1000 rhG-CSF. The rhG-CSF plus RA treated cells demonstrated significant increase in the percentage of mature cells. Morphological changes and nitroblue tetrazolium (NBT) reduction activity evidenced more increase than RA treatment alone (P less than 0.001). The results suggest that RA not only inhibits the proliferative action of G-CSF, but also retains and enhances the action of G-CSF to induce differentiation. Therefore, we believe that the combined use of G-CSF with RA may improve the treatment of leukemia.     

c-Myb在急性早幼粒细胞白血病发病过程中的作用

目的探讨转录因子c—Myb在急性早幼粒细胞白血病（APL）发病过程中的作用。方法通过分析患者的表达谱数据,比较在正常早幼粒细胞和APL细胞中c—Myb的表达水平;然后通过全反式维甲酸（ATRA）诱导NB4细胞分化和PR9加ZnSO4模拟APL发病,研究c—Myb是否参与APL发病过程;利用RNAi干扰c—Myb表达的技术,明确c—Myb对逆转APL的作用。结果在APL细胞中c—Myb的表达水平高于正常早幼粒细胞;c—Myb的表达随着ATRA的诱导分化逐渐下降,在ZnSO。诱导PR9模拟APL发病的过程中逐渐上升;c—Myb的敲除可以促进NB4细胞的分化,使NB4细胞的CD11b阳性率增加约20％。结论APL细胞中c—Myb的表达高于正常早幼粒细胞,它对APL的发病有着重要的作用,对其选择性敲除可以部分逆转APL细胞的分化阻滞。     

The Experimental and Clinical Study on the Effect of Curcumin on Cell cycle Proteins and Regulating kProteins of Apoptosis in Acute Myelogenous Leukemia

Because anti- cancer drugs can induce apopto-sis of both carcinoma cells and normal cells,peoplewant to find a new high effect and low cytotoxinone.Curcumin( C12 H3 6O5,Fw364.5 ) derives fromcurcumin longa linn and contains a main activity ofcurcuma.It has excellent effect of anti- cancer andpreventing cancer.FDA in USA has recommendedit into a new candidated drug which is used in the2 1 th century[1] .The anti- cancer role of curcuminmay be two aspectes:( 1 ) It controls developmentproces…     

Protein kinase C in the promyelocytic leukemia cell differentiation of granulocytes.

When the leukemia cells in 14 patients with acute promyelocytic leukemia (APL) were induced by all-trans retinoic acid (RA) treatment, the activity of protein kinase C (PKC) increased with the differentiation. In the control cells, the activity of PKC was only 47 +/- 39.3 pmol.mg-1/min, while it was 149.3 +/- 150.1 pmol.mg-1/min after differentiation. There were 90.1 +/- 7.2% promyelocytes in the control group, and 8.9 +/- 5.6% in the induction group. Therefore, we think that there is a close correlation between PKC and the differentiation of promyelocytic leukemia cells.

     

ALL-TRANS RETINOIC ACID WITH OR WITHOUT LOW DOSE CYTOSINE ARABINOSIDE IN ACrlJTE PROMYELOCYTIC LEUKEMIA REPORT OF 6 CASES

This paper reports 6 cases of acute promyelocy- tic Ieukemia treated by all-trans retinoic acid (RA) with or without cytosine arabinoside (10 mg, IM, every 12 hours). All obtained complete remission. In vitro, bone marTOW leukemic promyelocytes from these patients matured morphologically in suspension culture with RA (1-5 µm). No changes took place in the controls. Chloroacetate esterase, alpha-na- phthyl acetate esterase stains and electron microsco- pic examination confirmed that RA-cultuted cells differentiated into granulocytes with increased func tional maturation (measured by nitroblue tetrazolium reduction). The data suggest that RA may be an effective drug in acute promyelocytic leukemia.     

维生素甲酸诱导人早幼粒细胞白血病细胞分化的研究

应用光镜、电镜、冰冻蚀刻复型、细胞化学、NOR银染等方法,分析了经维生素甲酸(RA)诱导后的人早幼粒细胞白血病细胞系(HL-60)及急性早幼粒细胞白血病(APL)患者骨髓粒细胞的结构及功能变化。结果表明,RA可以诱导HL-60细胞按粒系途径成熟分化,并证明RA对APL患者体内治疗的有效性。     

维甲酸和三氧化二砷治疗急性早幼粒细胞白血病的现状

急性早幼粒细胞白血病 (APL)是具有生物学和临床特点的一种特殊类型急性髓细胞白血病。近年来全反式维甲酸 (ATRA)的应用极大地提高完全缓解率和减少了治疗相关死亡率。ATRA与化疗联合应用有助于降低复发率和延长生存期。三氧化二砷 (As2 O3 )治疗初治和复发APL已取得巨大成功。持续分子缓解是APL的治疗目标。早期发现分子复发并给予补救治疗 ,可取得更好的临床治疗效果