THE CLINICAL SIGNIFICANCE OF MULTIDRUG RESISTANCE GENE(mdr1) EXPRESSION IN ACUTE LEUKEMIA

ＴＨＥＣＬＩＮＩＣＡＬＳＩＧＮＩＦＩＣＡＮＣＥＯＦＭＵＬＴＩＤＲＵＧＲＥＳＩＳＴＡＮＣＥＧＥＮＥ（ｍｄｒ１）ＥＸＰＲＥＳＳＩＯＮＩＮＡＣＵＴＥＬＥＵＫＥＭＩＡＤｏｎｇＺｕｏｒｅｎ董作仁ＬｕｏＪｉａｎｍｉｎ罗建民ＸｕＷｅｎｘｉｎ徐文新ＷａｎｇＦｕｘｕ...     

DETECTION AND ITS CLINICAL VALUE OF MINIMAL RESIDUAL DISEASES IN ACUTE PROMYELOCYTIC LEUKEMIA

It has been demonstrated that minimal residualdisease (MRD) in leukemia after complete remission(CR) was related to the relapses[1]. The detection of MRD also can be used as a indicator to direct the further intensive chemotherapy in post-remission treatment[2]. The best example of MRD detection in current hemotology practice is the RT/PCR for the BCR-ABL fusion mRNA in CML after bone marrow transplantation[3]. Acute promyelocytic leukemia(APL) is characterized by the presence of …     

PROGNOSTIC SIGNIFICANCE OF EXPRESSION OF SURVIVIN IN ACUTE LEUKEMIA

Leukemia, one of the most common cancer, is diagnosed via morphology and immunophenotype, and it抯 incidence continues to rise. Although bone marrow transplantation and combination chemo- therapy have improved the outcome, many patients do not achieve complete remission (CR) and they ultimately relapse. In particular, acute leukemia (AL) is associated with poor prognosis and often runs a fulminant course. Regulated programmed cell death (Apoptosis) maintains normal homeostasis and organ mor…     

EXPRESSION OF THE MULTIDRUG RESISTANCE GENE IN LEUKEMIC CELLS

P-glycoprotein(Pgp; Mr=170,000) to encoded by a family of genes-Multldrug resistance gene. The Pgp has been demonstrated to mediate resistance to multiple structurally dissimilar drugs, which fuctions as an energy- dependent efflux pump so that a cell with high level of mdr expression can more effectively eliminate cytotoxic drugs. In this report, a simplified method for analysis of clinical samples and assess the level of gene expression was set up. Furthermore, by using 32P labelled mdr- 1 cDNA as the probe and RNA dot blotting the mdr-mRNAs from 5 cases of myeloblastic leukemia cells were analysed. It was shown that the level of mdr-1 expression In different myeloleukeic cells was various and reduced In one case after remission. The established method for mRNA analysis could be generalized for evaluating the level of mRNA in clinical samples.     

A CLINICAL AND ULTRASTRUCTURAL STUDY OF ACUTE ESOINOPHILIC LEUKEMIA

The present study analyses two cases with acuteimmature eosinophilic leukemia. The clinical, physical,laboratory and pathologic materials are discussed.There is an abnormal number of immature eosinophiliccells in the blood and bone marrow, usually accompaniedby anemia and thrombocytopenia. Especially the ultra-structural features include abnormal granules, asyn-chronous maturation of the nucleus and cytoplasm,dilated endoplasmic reticulum and more Conspicuousnucleoli. Differential count was more precise underelectron microscope than under light microscope. Thesefindings may be helpful for differential diagnosis andclassification.     

PURGING OF ACUTE NON-LYMPHOCYTIC LEUKEMIA PROGENITORS BY PROCAINE AND HYPERTHERMIA

Procaine and hyperthermia have been shown to possess a relatively selective cytotoxicity to leukemlc cells. In this study, the combined effects of procaine and hyperthermia on the growth of hematopoietic progenitors (GM-CFU) and ieukemic progenitors (L-CFU) were examined to determine if this combination resulted in a great selective killing of leukemlc cells than that achieved by procaine or heat alone. When the cells were treated simutaneously with procaine (2 mM) and hyperthermia (42℃) for one hour, the killing of L-CFU was enhanced considerably whereas GM-CFU were not markedly affected. These data Indicate that the combined treatment with procain and hyperthermia might offer an efficient mean to selectively purge residual leukemlc cells in vitro. Procaine with hyperthermia may have a role in clinical autoiogous bone marrow transplantation for acute leukemia.     

PRIMARY PLASMA CELL LEUKEMIA(A COMPREHENSIVE ANALYSIS OF 44 CASES)

Four cases of primary plasma cell leukemia (PPCL) admitted to Zhongshan Hospital from 1959 to 1987 are reported with a review on additional 40 cases reported in China. Comparing with the 57 cases of multiple myeloma (MM) treated in our hospital, the following features were observed in PPCL: (1) The age was younger, with a mean of 45.2 years, 34.1% of the patients were under 40 years. (2) Onset was abrupt. Duration from onset to diagnosis was 2 months or less in 77% patients but never beyond 6 months. (3) 81.8% patients had liver enlargement, 59.1% splenomegaly and 61.4% sternum tenderness. (4) All patients showed marked anemia with an average hemoglobin of 65 g/L. BPC count was less than 100 × 109/L in 76% patients and WBC was more than 10×109/L in 77%. (5) Plasma cell number in the marrow was markedly increased with an average of 69%, of which the blast cells and immature forms were predominant. (6) No destruction of bones was shown on X-ray film in 68.3% patients. (7) The response to chemotherapy wa     

CENTRAL NERVOUS SYSTEM RADIOTHERAPY IN ACUTE LEUKEMIA

From Dec. 1976 through June 1986, 474 patients with acute leukemia were treated with central nervous system (CNS) irradiation for the purpose of preventing relapse of CNS leukemia. Of the whole series, whole cranial irradiation at a dosage of 24 Gy and 4-5 intrathecal instillations of methotrexate (MTX) were given in 149 patients, simple intrathecal instillation of MTX in 44 patients and high dose intravenous MTX in 5 patients; the CNS relapse rates were 4.0%, 20.5% and 40.0% respectively. It was proved by our experience that whole cranial irradiation plus intrathecal MTX is the best approach to prevention of CNS leukemia relapses.     

INFLUENCE OF NEOADJUVANT INTRAARTERIAL INFUSION CHEMOTHERAPY ON APOPTOSIS AND MULTIDRUG RESISTANCE ASSOCIATED GENES OF ENDOMETRIAL CANCER

Many researches have proved that neoadjuvantintraarterial infusion chemotherapy (NIAC) is a useful method for the treatment of uterine cervical cancer[1, 2]while there are few reports about endometrial cancer[3Apoptosis has been shown to occur in various tumors in response to chemotherapeutic agents. It is not only related to the tumor response to chemotherapy, but also closely associated with the multidrug resistance[4, 5]. To date, no data have become available that shed light on the timin…     

急性白血病患者多药耐药基因mdrl的表达及其临床意义

目的　探讨白血病细胞的抗药性与化疗效果及预后的关系。方法　采用逆转录 -聚合酶链反应 ( RT- PCR)的方法检测了 85例不同时期急性白血病 ( AL)患者多药耐药基因 mdrl m RNA的表达 ,同时检测了 2 0例正常人作为对照。结果　初治组 mdrl的阳性率为 4 4 .7% ,mdrl 与 mdrl-患者的完全缓解 ( CR)率分别为 2 3.9%和 88.5% ( P<0 .0 0 5) ,复发及难治组患者 mdrl的阳性率明显高于CR组 ( P<0 .0 0 1) ,复发及难治组 mdrl m RNA的表达水平也高于 CR组 ( P<0 .0 0 1)。CR患者 mdrlm RNA的表达水平逐渐升高可导致临床复发。正常人和长期生存患者 mdrl的阳性率很低。另外发现mdrl的表达与法、美、英协作组 ( FAB)分型有关。结论　mdrl的表达与 AL的化疗效果及预后密切相关 ,它是 AL患者一个重要的不利预后因素。     

抗凋亡基因bcl-xL与白血病细胞耐药的相关性研究

目的 研究ｂｃｌ－ＸＬ基因高表达的白血病细胞耐药形成中的作用,观察急性髓细胞白血病病人的ｂｃｌ－ＸＬ表达与临床疗效间的相关性。方法 采用脂质体法将ｂｃｌ－ＸＬ ｃＤＮＡ转导入ＨＬ－６０细胞;流式细胞仪定量检测凋亡细胞：ＭＴＴ法测定足叶乙甙、柔红霉素、阿霉素对转染细胞的细胞毒性;ＲＴ－ＰＣＲ法检测２０例急性髓细胞白血病病人的ｂｃｌ－ＸＬ表达。结果 ｂｃｌ－ＸＬ高表达可抑制足叶乙甙诱发的凋亡,抑制率为     

急性早幼粒细胞白血病耐药机制的研究进展

全反式维甲酸(ATRA)与三氧化二砷(As2O3)作为一线药物治疗急性早幼粒细胞白血病(APL)以来,APL患者的治愈率得到显著提高.但ATRA和(或)As2O3耐药的出现成为一个严重问题.现就近年来新提出的一些耐药机制如融合基因突变、细胞信号通路异常、染色质重构复合物异常、凋亡调控异常、骨髓微环境介导耐药等方面进行综述.     

多药耐药功能实验对急性白血病化疗疗效的预测意义

背景与目的:多药耐药排药蛋白P-糖蛋白(P-glycoprotein,P-gp)在介导急性白血病多药耐药中的作用已得到公认。多项研究显示,P-gp及其编码基因MDR1mRNA的表达与白血病化疗疗效相关,但我们在临床实践中所获得的结果却并非如此。近年来多项研究发现,多药耐药功能实验结果比P-gp的表达水平对预测化疗疗效更有价值。为了解P-gp的表达和多药耐药功能实验对判断患者预后的价值,我们对24例初诊未治急性白血病患者白血病细胞膜P-gp的表达以及功能活性进行了检测,以探讨多药耐药功能试验对化疗疗效的预测价值。方法:用流式细胞仪测定24例急性白血病患者白血病细胞的P-gp表达率以及反映MDR功能的Rh123排出实验和细胞内柔红霉素蓄积实验的MIR值,并就患者的化疗疗效进行分组比较和相关分析。结果:CR患者初诊时白血病细胞P-gp表达率为(2.16±2.42)%,与NR患者犤(15.02±25.88)%犦差异无显著性(P=0.114)。CR患者初诊时白血病细胞Rh123排出实验的MIR值:MIR(RE)(1.16±0.38)明显低于NR患者(1.43±0.26)(P=0.045)。CR患者初诊时白血病细胞内柔红霉素积蓄实验的MIR值:MIR(IDA)(1.02±0.05)亦明显低于NR患者(1.47±0.44)(P=0.005)。MIR(RE)(r=0.590,P=0.006)和MIR(IDA)(r=0.867,P=0.000)与疗效间有显著相关性。P-gp表达率与疗     

川芎嗪联合环胞霉素A逆转白血病多药耐药的研究

目的：寻找有效的多药耐药联合逆转剂。方法：用逆转录－聚合酶链反应（ＲＴ－ＰＣＲ）,Ｗｅｓｔｅｒｎ ｂｌｏｔ和ＭＴＴ法研究芎嗪逆转耐药细胞系ＨＬ－６０／ＶＥＲ的作用,对多种化疗药物耐药的白血病用川芎嗪与环孢菌素Ａ（ＣｓＡ）加化疗药物联合用于治疗２１例复发难治性白血病。结果：单用川芎嗪在体外能不同程度地增加ＨＬ－６０／ＶＣＲ细胞对多种化疗药物的敏感性,降低Ｐ１７０蛋白的表达。川芎嗪联合不胞素Ａ有较好逆     

RNA干扰及其在白血病多药耐药方面的研究进展

 白血病化疗失败的主要原因是白血病细胞的多药耐药，这是困扰临床肿瘤化疗的难题之一。RNAi是新近发展起来的一种全新的基因治疗手段。与常用的反义RNA技术等其他基因方法相比，具有经济、高效、高度特异性、操作简便、快速等优点。该技术为白血病多药耐药的基础和临床研究开辟了新思路，也为新的分子诊断和分子治疗提供可能。     

HA117在成人急性白血病中的表达及意义

目的 检测HA117基因在急性白血病患者骨髓单个核细胞(BMMNC)中的表达,探讨其与多药耐药的关系及与抗原表达的相关性及临床意义。方法 应用逆转录聚合酶链反应(RT-PCR)方法检测14例不同时期急性淋巴细胞白血病(ALL)患者和36例急性髓系白血病(AML)患者BMMNCHA117基因表达;以10例特发性血小板...     

儿童急性白血病初治患者LRP和MRP的表达及其临床意义

背景与目的:有研究发现肺耐药相关蛋白(lungresistanceprotein,LRP)和多药耐药相关蛋白(multidrugresistance鄄associatedporotein,MRP)的表达与白血病患儿耐药有关,而且患儿耐药不是由于一种耐药机制引起的。本研究旨在观察LRP和MRP在不同类型小儿白血病初治时的表达情况及其与临床疗效的关系。方法:应用逆转录鄄聚合酶链反应法(RT鄄PCR)检测38例不同类型儿童急性白血病[27例急性淋巴细胞白血病(acutelymphoblastic,ALL),11例急性非淋巴细胞白血病(acutenonlymphocyticleukemia,ANLL)]及6名正常儿童LRP、MRP基因的表达,结合患儿化疗后的完全缓解(CR)率分析两种基因表达的意义。结果:38例患儿化疗后CR26例(68.4%)。38例患儿中LRP基因表达阳性11例(28.9%),表达阴性27例(71.1%),6例正常对照儿童LRP基因阴性。LRP基因阳性患儿的CR率低于阴性者(分别为27.3%和85.2%,P<0.05)。MRP阳性者21例,6例正常对照儿童MRP基因阴性。MRP基因阳性者的CR率低于阴性者(分别为47.6%和94.1%,P<0.05)。27例ALL患儿中LRP阳性5例,11例ANLL患儿中LRP阳性6例(分别为18.5%和54.5%,P<0.05)。27例ALL患儿中MRP阳性16例;11例ANLL患儿MRP阳性5例(分别为59.3%和45.5%,P>0.05),ALL和ANLL中MRP的表达无显著性差异。LRP基因阳性患者的MRP阳性率与LRP阴性者MRP阳性率无显著性差异(分别为28.6%和29.4%,P>0.05),说明LRP基因与MRP基因之间无相关性。结论:LRP基因及MRP基因阳性儿童急性白血病者病情重、化疗缓解率低,儿童ANLL相对于ALL化疗缓解率低可能与LRP的表达有关。     

高通量分析技术在肿瘤MDR中的研究进展

高通量分析技术是近年来肿瘤研究新平台,肿瘤多药耐药(MDR)和耐药逆转药物研究在肿瘤化疗领域亟需解决。现综述基因芯片、蛋白质芯片、组织芯片三大高通量微阵列技术在肿瘤MDR机制、筛选耐药逆转靶点和逆转药物及指导临床个体化治疗等方面的应用。