急性淋巴细胞白血病患儿肺耐药蛋白表达及临床意义

应用免疫组化法 ,对 2 7例初治和 2 1例复发及难治的急性淋巴细胞白血病 (AL L )患儿检测外周血或骨髓中白血病细胞的肺耐药蛋白 (L RP)表达情况 ,同时体外应用 MTT方法观察了所有患儿的白血病细胞对柔红霉素 (DNR)化疗的敏感性。结果 :2 7例初治患儿的 L RP表达率为 18.5 % ,2 1例复发及难治患儿的 L RP表达率为 6 6 .7% ,两者比较 P<0 .0 1。在 2 7例初治患儿组中 ,L RP表达阴性者对 DNR的敏感率为 86 .4 % ,L RP表达阳性者为 2 0 % ,两者比较 P<0 .0 1;在 2 1例复发及难治患儿中 ,L RP表达阴性者对 DNR敏感率为 2 8.6 % ,L RP表达阳性者为 2 1.4 % ,两者比较 P>0 .0 5。在 2 7例初治组患儿中 ,L RP表达阴性者的 CR率为 90 .9% ,L RP表达阳性者为 6 0 % ,两者比较 P<0 .0 1;在 2 1例复发及难治患儿中 ,L RP表达阴性者的 CR率为 4 2 .9% ,L RP表达阳性者为 5 0 % ,两者比较 P>0 .0 5。认为 L RP可能是产生多药耐药 (MDR)的另外一个重要因素     

急性白血病患者肺耐药相关蛋白检测及临床意义

目的：探讨急性白血病（AL）患者肺耐药相关蛋白（LRP）的表达与临床病情和疗效的关系.方法：采用免疫细胞化学方法（SABC）检测57例AL患者及14例对照组骨髓单个核细胞LRP的表达.结果：①AL初治组LRP表达阳性率（30.00%）与完全缓解组阳性率（25.00%）比较差异无统计学意义（P＞0.05），难治复发组LRP表达阳性率（61.90%）较完全缓解组与初治组明显增高（均P＜0.05）.②37例化疗后AL患者LRP阳性表达17例，LRP阴性表达20例，LRP阴性组缓解率显著高于阳性组（P＜0.05）.结论：AL患者LRP高表达与临床耐药有关，有可能成为判断预后的一个重要因素。     

PTTG蛋白在急性白血病中的表达及意义

垂体肿瘤转化基因(PTTG)是近年来从垂体组织中分离的原癌基因,其在多种肿瘤组织及部分正常组织细胞内高度表达,对促进细胞增殖、转化和肿瘤发生有重要的作用。2003年12月至2004年7月,我们采用免疫细胞化学方法对53例急性白血病患者进行了PTTG基因表达检测,以探讨其临床意义,为急性白血病的诊断、疗效评价及预后估计提供参考指标。     

肺耐药蛋白基因在多发性骨髓瘤中的表达及意义

到目前为止 ,多发性骨髓瘤 (MM )的治疗仍以化疗为主 ,但是治疗效果并无质的飞跃 ,多药耐药的产生可能是一条重要的原因 ,肺耐药相关蛋白 (LRP)基因于 1995年被克隆并定位 ,我们用半定量逆转录 -聚合酶链反应 (RT PCR)方法检测了 4 1例MM患者LRP基因的表达 ,探讨其表达与化疗反应及预后的关系 ,旨在进一步研究MM的耐药机制 ,指导其治疗。一、资料与方法1.对象 :所有标本均收集自 1998年 1月 1日～ 2 0 0 0年5月 1日青岛医学院附属医院门诊及住院患者 ,其中初治MM 2 1例 ,男 13例 ,女 8例 ,年龄 2 8～ 78岁 ;复治MM 2 0例 ,男 10例 …     

急性髓系白血病生存素、多药耐药基因与肺耐药基因的表达及其临床意义

目的：探讨初治急性髓系白血病(AML)细胞生存素(Survivin,S)、多药耐药基因(mdr-1)与肺耐药蛋白(LRP)表达与疗效的关系。方法：应用RT—PCR法检测46例初治AML患者的S、mdr-1和LRP mRNA表达的阳性率。结果：46例AML患者细胞S mRNA阳性率为69．6％，mdr-l mRNA阳性率为52．2％，均分别高于正常对照组(27．8％，11．1％，P＜0．01)，而表达LRP阳性率与正常对照组差异无显著性意义，分别为36．9％和16.7％(P＞0.05)。S阳性者CR(62．5％)明显低于阴性者(92．9％，P＜0.05)。mdr—1阳性者CR(45．8％)明显低于阴性者(100％，P＜0．01)。LRP阳性者CR(41．2％)明显低于阴性者(89．7％，P＜0.01)。S和mdr—1双阳性者CR(45.5％)明显低于双阴性者(100％，P＜0．01)。S和LRP双阳性者CR(35．7％)明显低于双阴性者(100％，P＜0．01)。结论：S、mdr-l和LRP可作为独立预后因素。S和mdr-l或S和LRP双阳性者CR率明显减低。     

急性白血病乳腺癌耐药蛋白基因表达及其与临床的关系

化疗是急性白血病 (AL)的主要治疗手段。耐药是影响化疗疗效的重要因素 ,目前认为AL耐药即多药耐药 (MDR)的发生是多因素、多种机制作用的结果[1,2 ] 。乳腺癌耐药蛋白基因 (BCRP)是 1998年才被发现的又一与耐药有关的糖蛋白 ,它主要参与膜内、外药物转运而改变药物在胞内的分布 ,以药物排出泵的作用参与MDR[3 ] 。有关BCRP与AL临床的关系报道极少 ,为探讨BCRP在成人AL中的表达及其与临床关系 ,本研究应用半定量逆转录 PCR(RT PCR)检测AL患者的BCRP表达 ,并结合mdr 1、耐药相关蛋白基因 1(MRP 1)及肺耐药蛋白基因(LRP)…     

急性白血病患者细胞周期蛋白B1表达与耐药的关系

目的　探讨细胞周期蛋白B1 (cyclinB1 )在急性白血病 (AL)中的表达以及与耐药的关系。方法　本研究对 85例初治AL患者 (其中敏感组 47例 ,耐药组 38例 )及 1 7例正常人采用流式细胞术检测cyclinB1、p1 70蛋白表达水平。采用半定量逆转录 聚合酶链反应 (RT PCR)检测cyclinB1、多药耐药基因 1 (mdr 1 )、DNA拓扑异构酶Ⅱ的两个同工酶TOPOⅡα、TOPOⅡβ以及bcl 2的mRNA水平。结果　 (1 )耐药组cyclinB1蛋白 (M =1 2 3 % )和mRNA (M =0 2 1 7)以及TOPOⅡα(M =0 2 36)、TOPOⅡβ(M =0 32 8)的mRNA表达水平明显低于敏感组cyclinB1蛋白 (M =2 2 7% )和mRNA (M =0 563)、TOPOⅡα(M =0 51 4 )、TOPOⅡβ(M =0 635) (P <0 0 1 )。全部正常人cyclinB1蛋白的表达水平 <5 % ,在相同条件下未检出cyclinB1、TOPOⅡα、mdr 1的mRNA表达。 (2 )耐药组患者的p1 70蛋白 (M =1 4 3 % )及mdr 1 (M =1 0 71 )、bcl 2 (M =0 941 )的mRNA表达水平明显高于敏感组p1 70蛋白 (M =3 6 % )、mdr 1 (M =0 0 94)和bcl 2 (M =0 1 53)的mRNA表达水平 (P <0 0 1 )。 (3)cyclinB1蛋白与TOPOⅡα、TOPOⅡβ的mRNA表达呈正相关 (rTOPOⅡα=0 472 ,P <0 0 1 ) ;(rTOPOⅡβ=0 683 ,P <0 0 1 ) ;cyclinB1mRNA与TOPOⅡα     

急性早幼粒细胞白血病骨髓白血病细胞P-gp及MRP和LRP的表达

多药耐药（MDR）的分子机制至今尚未完全被阐明，膜转运蛋白P-糖蛋白（P-gP）、多药耐药相关蛋白（MRP）和肺耐药蛋白（LRP）过度表达对于白血病治疗失败的影响至今仍是一个有争议的问题。急性早幼粒细胞白血病（APL）是一个具有特异形态学和细胞遗传学特征的在细胞生物学和临床方面被明确定义的一种白血病亚型。该病如果DIC能够被很好地控制，绝大多数患者可获得长期完全缓解（CR）。因此，我们应用流式细胞仪对49例APL患者骨髓白血病细胞P-gP、MRP和LRP的表达情况进行了评估，并对初治与难治复发患者之间膜转运蛋白表达的相关性亦进行了描述。     

耐药相关蛋白在肺癌组织中的表达及意义

目的　探讨耐药相关蛋白在肺癌组织中的表达及意义。方法　应用免疫组化法检测治疗前 90例肺癌组织标本中 P-糖蛋白 (P- gp)、多药耐药相关蛋白 (MRP)、肺耐药蛋白 (L RP)、谷胱苷肽 S转移酶 (GST- π)、DNA拓扑异构酶 (Topo- )蛋白的表达 ;流式细胞术检测肺癌组织增值指数 (PI)、DNA指数 (DI)及细胞周期各时相分布。结果　非小细胞癌 (NSCL C组 ) P- gp、L RP表达明显高于小细胞癌 (SCL C)组 (P <0 .0 5 ) ,MRP+L RP共表达者高于 SCL C组 (P <0 .0 5 ) ;中、高分化癌组 P- gp、L RP表达高于 SCL C组 (P <0 .0 5 ) ,MRP表达高于低分化癌组 (P <0 .0 5 ) ;腺癌组 MRP、L RP、MRP+L RP、MRP+L RP+GST- π、MRP+L RP+P- gp+GST-π表达高于鳞癌组、SCL C组、低分化癌组 (P <0 .0 5 ) ,MRP+GST- π共表达者高于鳞癌组、低分化癌组 (P <0 .0 1)。P- gp与 Topo 蛋白表达呈正相关 (P <0 .0 5 )。MRP与肺癌组织增殖指数 (PI)、G2 / M期细胞比例呈正相关 (P <0 .0 5 ) ,与 G0 / G1 期细胞比例呈负相关 (P <0 .0 5 )。结论　联检肺癌组织中耐药相关基因蛋白的表达有助于判断化疗疗效及预后。 P- gp、L RP、MRP、GST-π可作为判断肺癌细胞原发性耐药的指标。     

急性白血病患者雌激素受体多药耐药相关蛋白的检测及临床意义

目的 :探讨雌激素受体 (ER)、多药耐药相关蛋白 (MRP)表达与临床疗效的关系 ,为耐药白血病寻找新的治疗途径。方法 :采用免疫组化ABC法检测了 37例急性白血病 (AL)复发难治患者骨髓单个核细胞的ER与MRP表达。结果 :①ER阳性组CR率为 91.6 7% (11/ 12 ) ,阴性组为 2 8.0 0 % (7/ 2 5 ) ,ER阳性组CR率显著优于阴性组 (P <0 .0 1)。②MRP阳性组CR率为 2 3.81% (5 / 2 1) ,MRP阴性组为 81.2 5 % (13/ 16 ) ,MRP阳性组CR率明显差于阴性组 (P <0 .0 1)。③ 37例AL患者中 ,8例ER +/MRP -与 17例ER - /MRP +患者其ER与MRP表达的一致性很好 (Kappa系数 =0 .83,P <0 .0 1)。另有ER +/MRP +4例 ,ER - /MRP - 8例 ,其ER与MRP表达缺乏一致性。结论 :ER与MRP表达有一定的一致性 ,且与临床疗效有一定关系 ;ER与MRP检测有助于疗效和预后的判定     

Outcomes and charges of elderly patients with acute myeloid leukemia

A retrospective database analysis was conducted to evaluate hospitalization outcomes and charges among elderly acute myeloid leukemia (AML) patients. The data source was a longitudinal (2000-2003) inpatient database from 28 US hospitals. Data on 275 AML patients aged 60 and older were analyzed for demographic and treatment characteristics, hospital mortality, length of stay (LOS), overall days of stay (DOS), and charges across multiple admissions. Multivariate modeling was performed to determine factors that influenced outcomes. Overall, 115 (41.8%) patients received inpatient chemotherapy (CT); most (90.4%) received it on the first admission. Of all initial CT regimens 40.9% consisted of a single agent. The mean LOS for initial hospitalization was 23.0 (SD 21.8) days for patients who received CT and 6.7 (SD 7.5) days for those who did not. One quarter (25.3%) of initial hospitalizations resulted in death. On initial hospitalization, mean total charges were $113,118 (SD $220,417) for patients who received CT and $43,999 (SD $190,533) for those who did not; for both groups mean charges were higher than respective subsequent admission charges. Overall, in-hospital mortality did not differ significantly between on-CT and off-CT groups (43.5 and 38.8%, respectively). In multivariate modeling, CT was significantly associated (P < 0.0001) with increased charges and LOS. Elderly patients with AML incurred substantial hospital charges and inpatient mortality. The highest charges and a substantial number of deaths occurred during first admission. Although treatment with CT was associated with increased charges and days in-hospital, inpatient mortality in the two groups was found to be similar.     

Development of acute myelocytic leukemia in patients with Crohn's disease

Summary In our hospital within one year two patients with Crohn's disease were seen who developed an acute myelocytic leukemia. A review of the literature reveals eight previously reported patients with both Crohn's disease and leukemia. Six of the reported 10 patients have had acute myelocytic leukemia and, interestingly, three of them, including our two patients, have shown monocytic differentiation (FAB type M4). It has been suggested that the relative risk of leukemia, especially acute myelocytic leukemia, is increased in patients suffering from ulcerative colitis. More data of patients with Crohn's disease and acute leukemia are needed to evaluate the possible association between these diseases.     

The treatment of acute myelocytic leukemia in patients 30 years of age and younger

The treatment of acute myelocytic leukemia in childhood and young adults has lagged behind that for acute lymphocytic leukemia. The studies described here were directed towards evaluating the role of intensive chemotherapy in the treatment of this illness. Intensive remission induction therapy combining cytosine arabinoside with an anthracycline antibiotic produced a complete remission rate comparable to that achieved in acute lymphocytic leukemia (45 of 49 patients or 92%). Intensive consolidation chemotherapy produced a median duration of complete remission of 160 weeks with 40% of patients projected to be in remission at 4 years. By contrast, the median duration of remission for patients treated with moderate consolidation/maintenance therapy was 23 weeks with only 10% of patients in remission at 4 years. These studies demonstrate that intensive chemotherapy can be administered to pediatric patients and young adults and that this approach to therapy produces a high remission rate with a 3 year median duration of remission.     

Acute lymphocytic leukemia in children presenting with bone marrow necrosis

Bone marrow necrosis has been regarded as an indicator of very poor prognosis in malignant disease. The cause and incidence are unknown, and reports of treatment response are few. We describe four children with marrow necrosis at presentation with acute lymphocytic leukemia (ALL), all of whom entered remission with standard treatment showing complete marrow healing. The bleak outlook for patients with marrow necrosis based on early experience in adults with disseminated malignancy does not appear to apply to children with ALL. The incidence of marrow necrosis at diagnosis of childhood ALL is 1%.     

Roles of the bone marrow niche in hematopoiesis,leukemogenesis, and chemotherapy resistance in acute myeloid leukemia

ABSTRACT

Objectives: To summarize the effects of the bone marrow niche on hematopoiesis and leukemogenesis and discuss the chemotherapy resistance that can arise from interactions between the niche and leukemia stem cells.

Methods: We review the major roles of the bone marrow niche in cell proliferation, adhesion and drug resistance. The signaling pathways and major molecular participants in the niche are discussed. We also address potential niche-targeting strategies for the treatment of acute myeloid leukemia (AML).

Results: The bone marrow niche supports normal hematopoiesis and affects acute myeloid leukemia (AML) initiation, progression and chemotherapy resistance.

Discussion: AML is a group of heterogeneous malignant diseases characterized by the excessive proliferation of hematopoietic stem and/or progenitor cells. Even with intensive chemotherapy regimens and stem cell transplantation, the overall survival rate for AML is poor. The bone marrow niches of malignant cells are remodeled into a leukemia-permissive environment, and these reformed niches protect AML cells from chemotherapy-induced cell death. Inhibiting the cellular and molecular interactions between the niche and leukemia cells is a promising direction for targeted therapies for AML treatment.

Conclusions: Interactions between leukemia cells and the bone marrow niche influence hematopoiesis, leukemogenesis, and chemotherapy resistance in AML and require ongoing study. Understanding the mechanisms that underlie these interactions will help identify rational niche-targeting therapies to improve treatment outcomes in AML patients.     

非霍奇金淋巴瘤中肺耐药相关蛋白的表达及意义

目的 研究非霍奇金淋巴瘸（NHL）中肺耐药相关蛋白（LRP）的表达及其临床意义。方法 应用免疫组化S-P法检测43例NHL患者（其中初治病例32例,复发病例11例）和10例坏死增生性淋巴结炎患者组织中的LRP水平。结果 LRP在NHL患者中表达明显高于坏死增生性淋巴结炎患者（P〈0．05）,而且NHL复发组高于初治组（P〈0．05）。12例随访患者中LRP阴性者治疗效果优于LRP阳性者。结论 LRP过度表达与NHL临床耐药及疗效相关。     

55例老年人急性白血病治疗观察

目的针对老年人急性白血病治疗方法及化疗剂量选择的意见不一，探讨支持治疗、小剂量单药化疗及联合化疗的疗效及影响预后的因素。方法回顾性分析５５例老年急性白血病患者的治疗情况，统计其完全缓解（ＣＲ）率、生存期及影响因素。结果ＣＲ率：支持治疗组１２例，为０；小剂量单药组１７例，为１７．６％；联合化疗组２６例，为３８．５％。生存期：支持治疗组平均１３天，小剂量单药及联合化疗组分别平均５．９及６．２个月。结论仅用支持治疗疗效差，联合化疗的ＣＲ率高于小剂量单药化疗者，药物毒性无增加，但未能延长患者生存期。初诊时外周血幼稚细胞过高、血小板过低者ＣＲ率低。早期病死率高、放弃治疗者多，亦是影响ＣＲ率的因素。     

急性髓系白血病骨髓单个核细胞CD11a的表达及临床意义

目的:探讨淋巴细胞功能相关抗原-1(LFA-1)的α链CD11a在急性髓系白血病(AML)的表达情况及临床意义。方法:采用免疫酶标ABC法检测25例初治AML患者和8例血液系统非恶性肿瘤患者为对照的骨髓单个核细胞CD11a的表达,并追踪观察AML患者的疗效。结果:CD11a在AML患者骨髓单个核细胞的表达率(37.02±13.30)%,明显低于对照组(87.13±5.38)%(P<0.05)。化疗后未缓解组AML患者发病时骨髓单个核细胞CD11a的表达率(47.09±10.55)较完全缓解组(29.11±9.36)%高(P<0.05)。结论:CD11a在AML患者骨髓单个核细胞表达异常,可能与白血病细胞逃脱机体免疫监控及从造血微环境释出有关。检测AML患者骨髓单个核细胞CD11a的表达水平对AML的预后判断有一定意义。     

P-glycoprotein, lung resistance-related protein and multidrug resistance associated protein in de novo acute non-lymphocytic leukaemias: biological and clinical implications

P-glycoprotein (PGP), lung resistance-related protein (LRP) and multidrug resistance associated protein (MRP) expression and the blast cells' intracellular daunorubicin accumulation (IDA) were evaluated in 96 previously untreated cases of de novo acute non-lymphocytic leukaemia (ANLL). 47/96 patients (49%) were classified as PGP+ 44/ 96 (46%) as LRP+, and 8/96 (8%) as MRP+. The more frequent MDR clusters were PGP-/LRP-/MRP- (32/96 cases, 33%) and the PGP+/LRP+/MRP- (27/96 cases, 28%) followed by PGP+/LRP-/MRP- (15/96 cases, 16%) and PGP-/LRP+/MRP- (14/96 cases, 14%). A favourable karyotype was observed more frequently in PGP- and LRP-cases. A highly significant correlation was found between either PGP or LRP overexpression and leukaemic blast cell IDA. All the patients received standard induction and consolidation treatments containing MDR-related (idarubicin, mitoxantrone, etoposide) and other (arabinosyl cytosine) drugs. Multivariate analysis showed that PGP overexpression was significantly associated with a poor response to treatment, both in terms of primary resistance or shorter survival. Other independent prognostic factors were age and cytogenetics. LRP overexpression did not reach statistical significance, although for LRP+ cases the trend was unfavourable. Due to small numbers, no conclusion could be made regarding MRP overexpression, but 5/8 cases showed unfavourable karyotypic abnormalities, 8/8 had a defective IDA and 6/8 failed to achieve remission. This study showed that both PGP and LRP overexpression are common features in de novo ANLL at onset whereas MRP overexpression is more rare. It suggested that overexpression of one of the MDR related proteins was associated with a defective IDA, and confirmed that, in addition to age and cytogenetics, PGP retains an independent prognostic value. It also suggested that LRP did not affect clinical outcome when patients were treated with idarubicin or mitoxantrone and arabinosyl cytosine.