HOX11原癌基因的活化对儿童急性白血病预后的影响

目的:探讨HOX11原癌基因的活化对儿童急性白血病(acute leukemia,AL)预后的影响。方法:对HOX11原癌基因表达阳性和阴性的282例初治急性淋巴细胞白血病(acute lymphoblastic leukemia,ALL)及82例急性髓细胞白血病(acute mye-locytic leukemia,AML)患儿正规化疗后的治疗效应进行研究和分析。结果:在标危、中危、高危组ALL患儿的正规化疗中,HOX11原癌基因阳性表达患儿的复发或死亡率均明显高于表达阴性的患儿(分别为P<0.005,P<0.01,P<0.005);在AML患儿中,HOX11原癌基因阳性表达患儿的复发或死亡率虽与HOX11表达阴性患儿相比较差异无统计学意义P>0.05),但HOX11原癌基因活化的AML患儿临床化疗效果差。结论:HOX11原癌基因的活化可能影响AL的预后。     

急性白血病细胞肺耐药相关蛋白的表达及其临床意义

目的:研究急性白血病细胞肺耐药蛋白(lung resistance-related protein,LRP)的表达,观察其表达率与化疗缓解率的关系。方法:利用LRP单克隆抗体,采用流式细胞术(FCM)分别测定15位正常对照和79例急性白血病(a-cute leukemia,AL)患者LRP的表达率,并分析其表达的临床意义。结果:初治急性淋巴细胞白血病(acute lymphoblastic leukemia,ALL)组LRP的表达率为(29.29±6.72)%,高于初治急性髓细胞白血病(acute myelogenous leukemia,AML)组的(21.46±5.23)%,P=0.0182;复发/难治ALL组LRP的表达率为(41.18±9.06)%,也较复发/难治AML组的(30.44±11.51)%高,P=0.0154。复发/难治组LRP的表达率均高于相应的初治组,P值分别为0.0175和0.0138。急性白血病细胞LRP( )组的临床缓解率为30.8%,明显低于LRP(-)组的77.5%,P=0.0081。结论:复发/难治组LRP的表达率高于初治组,LRP过度表达与急性白血病患者的临床耐药及临床疗效密切相关。     

血清维生素B12水平与急性白血病的关联

目的：观察血清维生素B12（VitB12）的水平与急性白血病不同类型、不同疾病阶段的关联。方法：收集140例确诊为急性白血病的患者，其中急性髓系白血病（acute myeloid leukemia，AML）95例、急性杂合型白血病（hybrid acute leukemia，HAL）2例、急性淋巴细胞性白血病（acute lymphoblastic leukemia，ALL）43例，分成3组：初治组63例、第1次完全缓解（complete response，CR）组（CR1组）57例以及复发组20例。应用化学发光法检测3组患者血清VitB12的水平。结果：初治组中，血清VitB12水平的升高主要见于AML患者，尤其是M3患者。AML初治患者中血清VitB12水平升高者显著多于CR1的AML患者（P〈0．01）；AML复发患者中血清VitB12水平升高者也显著多于CR1组的AML患者（P〈0．01）。ALL初治患者与CRI患者相比，血清VitB12水平的差异无统计学意义（P〉0．05）；但ALL复发患者的血清VitB12水平升高者显著多于CR1的ALL患者（P〈0．01）。结论：VitB12是急性白血病的诊断指标之一，在急性白血病患者中存在血清VitB12水平的动态变化，血清VitB12水平的升高与疾病活动程度相关。     

急性髓细胞白血病儿童Wilms瘤基因1及其剪接异构体的表达及临床意义

目的:探讨急性髓细胞白血病(acute myeloblastic leukemia,AML)患儿骨髓细胞中Wilms瘤基因1(Wilms tumor gene1,WT1)及其剪接异构体WT1(17AA+)的表达及临床意义。方法:应用实时荧光定量PCR(real-time fluorescence quantitative-PCR,RFQ-PCR)检测112例次AML患儿不同阶段骨髓细胞中WT1和WT1(17AA+)mRNA的相对表达量,计算WT1(17AA+)/WT1的比值,并以同期30例非白血病患儿作为对照。结果:AML初诊组患儿的WT1和WT1(17AA+)mRNA相对表达量均明显高于非白血病对照组及缓解期患儿(P<0.05)。复发组患儿的WT1和WT1(17AA+)mRNA相对表达量与初诊组和耐药组相比,差异无统计学意义(P>0.05)。缓解组患儿的WT1(17AA+)/WT1比值明显低于初诊组、复发组和耐药组(P<0.05)。3例AML患儿的动态监测结果显示,临床耐药或复发患儿的WT1和WT1(17AA+)mRNA相对表达量以及WT1(17AA+)/WT1比值均呈持续高表达,或者表现为一过性下降后的再度上升。结论:WT1及WT1(17AA+)mRNA剪接异构体可能成为判断AML预后及临床治疗疗效的指标。     

RUNX1 异构体在急性白血病中的表达及临床意义

［摘要］ 目的:探讨RUNX1 异构体的表达与临床疗效、疾病预后的关系,以期为急性白血病的个体化治疗、预后判断及微小残留病（minimal residual disease,MRD）的监测提供有价值的实验依据。方法: 选择2012 年4 月至2013 年4 月于广东医学院（现为广东医科大学）附属医院血液内科住院的急性白血病初治患者88 例、复发患者10 例为研究对象。采用qPCR法检测急性白血病初治、复发患者以及对照组患者（非恶性白血病）RUNX1 异构体RUNX1a 和RUNX1b/c mRNA的表达水平,并追踪检测同一患者化疗前后RUNX1a 和RUNX1b/c mRNA表达水平的变化。结果: (1)AML初治组、复发组以及ALL初治组RUNX1a mRNA的表达水平较对照组升高(P<0.05),AML初治组RUNX1a mRNA的表达水平较ALL初治组升高(P<0.05)。(2)AML及ALL患者初治时RUNX1a 和RUNX1b/ c mRNA 的表达水平较化疗后完全缓解（complete remission,CR）时升高(P<0.05)。(3)比较初诊时的RUNX1a 和RUNX1b/c mRNA表达水平,半年内死亡与存活患者、首疗程化疗后CR组与NCR组、初诊时高白细胞组与非高白细胞组均无显著差异(P>0.05);AML-ETO 融合基因阳性患者RUNX1a 表达水平较阴性患者升高(P<0.05)。(4)急性白血病患者RUNX1a 和RUNX1b/c mRNA的表达水平随着化疗呈递减趋势,复发时又明显增高甚至超过初治状态。结论: RUNX1a 异构体参与了急性白血病的发病,并且与AML的复发相关;RUNX1a 和RUNX1b/c mRNA表达水平与临床疗效相关,与疾病预后无关,可作为疾病疗效判断的指标;动态监测RUNX1a 和RUNX1b/c 异构体的表达水平可以作为化疗后MRD监测的有效指标,用于评估疗效、早期识别复发风险。     

Livin 基因在儿童急性白血病中的表达及其意义

 目的 观察Livin基因在急性白血病患儿白血病细胞中的表达及其意义。方法采用半定量反转录聚合酶链反应(RT-PCR)方 法检测31例ALL及22例AML患儿白血病细胞Livin mRNA的表达水平,并以12例非白血病患儿为对照组。结果急性白血 病(AL)患儿白血病细胞Livin mRNA阳性表达率为60.3%。ALL组和AML组Livin mRNA阳性表达率分别为61.3%和59.1% ,两者比较差异无统计学意义,但均高于非白血病对照组(8.3%),并且Livin mRNA阳性患儿的缓解率明显低于阴性 患儿的缓解率。结论Livin基因的过度表达与AL的发病具有相关性,可作为AL的诊断、复发及预后判断的指标之一 。     

复发难治急性淋巴细胞白血病患者sorcin基因的检测及临床意义

目的:探讨复发/难治急性淋巴细胞白血病(acute lymphoblastic leukemia,ALL)患者可溶性耐药相关钙结合蛋白(sorcin)基因的表达及其与缓解率的关系。方法:采用Northern blot检测K562/A02细胞株sorcin基因表达,逆转录聚合酶链反应检测42例ALL患者、27例非白血病患者和健康人sorcin基因的表达水平,并分析sor-cin基因表达的临床意义。结果:ALL初诊组、缓解组和复发/难治组sorcin基因表达均明显高于对照组,t值分别为5.736、4.624和6.800,P值均<0.01。复发难治组sorcin基因过度表达明显高于初诊组和CR组,χ2=8.464,P=0.01。ALL患者临床耐药组sorcin基因阳性表达显著高于非临床耐药组,χ2=9.212,P<0.01;CR率非临床耐药组显著高于临床耐药组,χ2=41.28,P<0.01。结论:sorcin基因过度表达与ALL患者临床耐药密切相关,是影响预后的重要因素,可作为检测临床耐药和判断预后的指标之一。     

凋亡抑制蛋白XIAP在儿童急性白血病中的表达及其临床意义

目的探讨凋亡抑制蛋白XIAP在儿童急性白血病（AL）中的表达及其临床意义。方法54例AL患儿,其中初诊未治26例,治疗后完全缓解（CR）23例,复发5例。应用免疫组织化学方法检测其骨髓细胞XIAP蛋白表达。对照组为10例非恶性血液病且骨髓正常患儿。结果初诊未治AL患儿骨髓中XIAP蛋白表达水平高于缓解期（P〈0．05）和对照组（P〈0．05）,和复发组相比差异无统计学意义（P〉0．05）,且缓解期仍高于对照组（P〈0．05）;初诊未治AL患儿骨髓中XIAP蛋白水平在急性淋巴细胞白血病（ALL）和急性非淋巴细胞白血病（ANLL）组比较差异无统计学意义（P〉0．05）。结论XIAP蛋白在儿童AL患者中高表达,提示XIAP可能通过抑制肿瘤细胞的凋亡参与了儿童AL的发生、发展。     

XIAP及其相关因子1在急性淋巴细胞白血病中表达意义

目的:探讨X染色体连锁凋亡抑制蛋白(XIAP)及其相关因子(XAF1)在急性淋巴细胞白血病(ALL)中的表达及其临床意义,并评估其在临床治疗及预后中的价值。方法:采用病例对照研究,应用实时荧光定量聚合酶链反应(RQ-PCR)检测85例ALL患者骨髓标本中XIAP及XAF1的mRNA表达水平。结果:XIAP mRNA表达水平初诊ALL组高于CR组和对照组(P<0.05),而低于复发组(P<0.05),CR组表达水平高于对照组(P<0.05);而XAF1在ALL时呈低表达或不表达,CR组表达高于ALL其它组(P<0.05),与对照组差异无统计学意义(P>0.05)。XIAP及XAF1二基因表达水平在T系ALL与B系ALL,成人与儿童,男女性别之间表达水平差异无统计学意义(P>0.05)。XIAP/XAF1比值在ALL患者中初诊组和复发组明显高于对照组和缓解组(P<0.05),缓解组高于对照组(P<0.05)。结论:ALL患者XIAP基因高表达,而XAF1呈现低表达或不表达,提示XIAP可能通过抑制白血病细胞凋亡参与了ALL的发生发展,并与预后不良及治疗反应相关。ALL中XIAP与XAF1表达水平的不平衡,可能是ALL预后不良及复发的一项重要因素之一。抑制XIAP及上调XAF1基因来治疗ALL,将为ALL的基因治疗提供新思路。     

Twist-1基因在髓系白血病细胞中的表达及其作用

目的:检测Twist-1基因在白血病患者和造血系统恶性肿瘤细胞系中的表达情况,并探讨其高表达对髓系白血病细胞增殖和凋亡的影响.方法:用Real-time PCR检测急性髓系白血病(acute myeloid leukemia,AML)、急性淋巴细胞白血病(acute lymphoid leukemia,ALL)、慢性粒细胞白血病(chronic myeloid leukemia,CML)患者和正常人的骨髓单个核细胞对照以及造血系统恶性肿瘤细胞系中Twist-1 mRNA表达情况.构建Twist-1过表达及干扰载体,制备慢病毒并感染髓系白血病细胞系K562、U937、KG-1a,通过细胞计数实验、集落形成实验、流式细胞术、Annexin V/PI方法评价Twist-1对白血病细胞增殖、集落形成能力、周期、凋亡的影响.结果:Twist-1在AML及CML患者中的表达水平显著高于对照(均P＜0.05),而ALL患者与对照组没有显著差异(P＞0.05).在K562、U937、KG-1a中过表达及干扰实验证实,Twist-1高表达促进肿瘤细胞增殖、集落形成并抑制细胞凋亡;干扰Twist-1表达则效果相反.结论:Twist-1高表达于AML、CML髓系白血病细胞,并促进白血病细胞的增殖和抑制凋亡.     

Epigenetic inactivation implies independent functions for insulin-like growth factor binding protein (IGFBP)-related protein 1 and the related IGFBPL1 in inhibiting breast cancer phenotypes.

PURPOSE: To analyze epigenetic regulation of two related genes, insulin-like growth factor binding protein-related protein 1 (IGFBP-rP1) and IGFBPL1, and its significance as a determinant of clinical phenotypes in human breast cancer. EXPERIMENTAL DESIGN: We have investigated the expression and epigenetic regulation of IGFBP-rP1 and IGFBPL1 in human breast cancer cell lines and primary and metastatic carcinomas. RESULTS: Expression of IGFBP-rP1 and IGFBPL1 is down-regulated in breast cancer cell lines. Aberrant methylation in the CpG islands of each gene correlates well with loss of expression at the mRNA level. Analysis of methylation in DNA isolated from human primary breast tumors showed that methylation in either gene was associated with a worse overall survival (OS; P=0.008) and disease-free survival (DFS) following surgery (P=0.04) and worse DFS following adjuvant chemotherapy (P=0.01). Methylation of IGFBP-rP1 alone was associated with a trend toward decreased OS (P=0.10) and decreased DFS (P=0.25). Methylation in IGFBPL1 was clearly associated with worse OS (P=0.001) and DFS (P<0.0001). Methylation in either IGFBP-rP1 or IGFBPL1 was significantly associated with nodal disease (P<0.001). CONCLUSIONS: Expression of IGFBP-rP1 and IGFBPL1 is regulated by aberrant hypermethylation in breast cancer, implying that inactivation of these genes is involved in the pathogenesis of this malignancy. Analysis of methylation of these genes may have utility in prediction of clinical phenotypes, such as nodal disease and response to chemotherapy.     

Insulin-like growth factor binding protein-related protein 1 (IGFBP-rP1) is a potential tumor suppressor protein for prostate cancer.

Insulin-like growth factor binding protein-related protein-1 (IGFBP-rP1) has been shown to have decreased expression in the progression from benign to malignant prostate epithelial cells (V. Hwa et al., J. Clin Endocrinol. Metab., 83: 4355-4362, 1998). The present study was undertaken to determine the effects of the re-expression of IGFBP-rP1 in a cell line from a model of human prostate cancer, M12, in which IGFBP-rP1 expression had been demonstrated to decrease from the parent epithelial cell, P69, to the malignant subline, M12. An IGFBP-rP1 cDNA encoding the protein was transfected into M12 cells in a plasmid that resulted in constitutive-expression of IGFBP-rP1. Clones of transfected M12 cells were selected for low (L) and high (H) levels of expression, and the plasmid vector alone was transfected into M12 as a control. After transfection, there was a marked alteration in the morphology of the M12 cells such that the H clones had an elongated appearance when compared with the M12 control cells. The M12 clones overexpressing IGFBP-rP1 had a dose-related increase in population doubling time, decreased colony formation in soft agar, an increased propensity to undergo apoptosis in response to 6-hydroxyurea, and decreased tumor formation in male athymic, nude mice. These data suggest that IGFBP-rP1 may have a suppressive effect on prostate cancer development.     

Strong suppression of tumor growth by insulin-like growth factor-binding protein-related protein 1/tumor-derived cell adhesion factor/mac25

Insulin-like growth factor binding protein-related protein 1 (IGFBP-rP1) has been shown to induce cellular senescence or apoptosis of breast and prostate cancer cell lines in vitro. To examine whether IGFBP-rP1 acts as a tumor-suppressive protein in vivo, we established two model systems. Expression of IGFBP-rP1 in the human bladder carcinoma cell line EJ-1 was blocked by RNA interference. Human colon cancer cell line DLD-1, which did not express endogenous IGFBP-rP1, was transfected with an IGFBP-rP1 expression vector. When injected intraperitoneally or subcutaneously into nude mice, the IGFBP-rP1-expressing EJ-1 and DLD-1 cell lines grew poorly, whereas the IGFBP-rP1 non-producers grew rapidly and produced large tumors. In monolayer culture the IGFBP-rP1 producers and non-producers grew similarly in each model, whereas in soft agar culture the former produced far less colonies than the latter. The IGFBP-rP1 producers had IGFBP-rP1 bound to the cell surface, and adhered more efficiently to fibronectin and laminin-5 than the respective non-producers. Expression of IGFBP-rP1 did not affect the efficiency of insulin signaling. These results demonstrate that IGFBP-rP1 strongly suppresses tumor growth by an insulin-independent or insulin-like growth factor-independent mechanism. Cell surface IGFBP-rP1 may reduce the anchorage-independent growth ability, leading to the marked loss of tumorigenicity.     

Human prostate cancer expresses the low affinity insulin-like growth factor binding protein IGFBP-rP1.

Many of the alterations in the insulin-like growth factor (IGF) axis in prostatic disease have been associated with changes in the insulin-like growth factor binding proteins (IGFBPs), a multigene family of proteins that are thought to mediate the action of IGFs on target tissues. IGFBP-related protein 1 (rP1), also known as IGFBP-7 or mac25, is a recently described member of the IGFBP family, the biological function of which has yet to be completely ascertained. In this study, we analyzed the localization of IGFBP-rP1 in prostate cancer and benign prostate tissues using immunohistochemistry and a polyclonal antibody, T1A12, that is specific for IGFBP-rP1. The most intense staining was observed in nerves, whereas smooth muscle cells in the prostate stained weakly. Lymphocytes were always negative. When normal prostatic secretory epithelium was present, staining was usually absent. The lining secretory epithelium stained positively in 0 of 12 (0%) cases of benign prostatic hyperplasia, 57 of 63 (90.5%) primary adenocarcinomas, and 7 of 7 (100%) prostate cancer metastases. Prostatic intraepithelial neoplasia showed a similar pattern of staining to that observed for the invasive tumors. Analysis of Northern blots showed that none of the prostate cancer cell lines (LNCaP, C4, C4-2, C4-2B4, 9069E3, DU145, and PC3) expressed IGFBP-rP1 mRNA. This lack of expression was confirmed by immunohistochemistry of s.c.-generated tumor xenografts of LNCaP and C4-2 and by immunoblot on serum-free-conditioned media from all prostatic cell lines. In contrast to these results, tumor xenografts generated by direct intraosseous injection of LNCaP or C4-2 to bone marrow space resulted in tumors that stained positively for IGFBP-rP1. Our results show that IGFBP-rP1 is expressed in both in situ and invasive prostate neoplasms, but not typically in normal secretory or BPH epithelium; furthermore, the expression of IGFBP-rP1 can be induced in human prostate cancer cell lines in vivo on interaction with an appropriate host environment.     

Downregulation of the potential suppressor gene IGFBP-rP1 in human breast cancer is associated with inactivation of the retinoblastoma protein, cyclin E overexpression and increased proliferation in estrogen receptor negative tumors.

The complex insulin-like growth factor network of ligands, receptors and binding proteins has been shown to be disturbed in breast cancer. In addition to defects in proteins controlling cell cycle checkpoints, this type of aberrations could affect tumor growth and survival thereby influencing both tumor aggressiveness and potential response to treatments. We have previously identified the T1A12/mac25 protein, which is identical to the IGFBP-rP1, as a differentially expressed gene product in breast cancer cells compared with normal cells. Here we compare the expression of IGFBP-rP1 in 106 tumor samples with known status of cell cycle aberrations and other clinicopathological data. This was done using a tumor tissue section array system that allows for simultaneous immunohistochemical staining of all samples in parallel. Cytoplasmic staining of variable intensity was observed in most tumors, 15% lacked IGFBP-rP1 staining completely, 20% had weak staining, 32% intermediate and 33% showed strong staining. Low IGFBP-rP1 was associated with high cyclin E protein content, retinoblastoma protein (pRb) inactivation, low bcl-2 protein, poorly differentiated tumors and higher stage. There was a significantly impaired prognosis for patients with low IGFBP-rP1 protein tumors. Interestingly, IGFBP-rP1 showed an inverse association with proliferation (Ki-67%) in estrogen receptor negative tumors as well as in cyclin E high tumors suggesting a separate cell cycle regulatory function for IGFBP-rP1 independent of interaction with the estrogen receptor or the pRb pathway.     

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。     

Neuroendocrine-like differentiation of non-small cell lung carcinoma cells: regulation by cAMP and the interaction of mac25/IGFBP-rP1 and 25.1

The need to develop more effective therapies for lung cancer has led to investigations in understanding the molecular mechanisms of the differentiation process, in particular neuroendocrine (NE) differentiation. Recent studies have demonstrated that NE differentiation in non-small cell lung carcinoma (NSCLC) is not uncommon. Those NSCLCs with NE differentiation are considered a form of in transition NE carcinoma and show a more aggressive clinical course compared with NSCLC without NE differentiation. 25.1, a novel protein interacting with mac25/insulin-like growth factor-binding protein-related protein 1 (mac25/IGFBP-rP1), induced NE-like differentiation when collectively overexpressed in M12 prostate cancer cells. We have examined mac25/IGFBP-rP1 and 25.1 as potential molecular regulators in vitro of the NE-differentiation process in lung cancer. In a panel of SCLC and NSCLC cell lines, mac25/IGFBP-rP1 and 25.1 were expressed at higher levels in SCLC. An increase and sustained activation of adenosine 3',5'-cyclic monophosphate (cAMP) levels induced NE-like differentiation in NSCLC cell lines, and a concomitant increase in the expression of mac25/IGFBP-rP1 and 25.1 was observed during the cAMP-regulated differentiation of NCI-H157 cells, suggesting the involvement of these proteins. Furthermore, the collective overexpression of mac25/IGFBP-rP1 and 25.1 in NSCLC cells induced NE-like differentiation as early as 6 h postinfection. The present data suggest that mac25/IGFBP-rP1 and 25.1 may play a functional role in the NE differentiation of NSCLC cell lines and may provide a novel therapeutic target for treating lung cancers, in particular NSCLC with NE differentiation.     

急性白血病耐药蛋白表达与临床疗效及预后的关系

目的:研究急性白血病(AL)耐药蛋白表达与临床疗效及预后的关系。方法:采用免疫组化法对40例初发AL耐药蛋白PGP、MRP1的表达进行检测,并分析其与病人预后的关系。结果:PGP表达阳性的AL中CR率36.36%,PGP表达阴性的AL中CR率92.85%(P<0.01);MRP1表达阳性的AL中CR率44.44%,MRP1表达阴性的AL中CR率为95.45%(P<0.01);PGP、MRP1同时表达阳性,CR率42.85%,全阴性的AL,CR率100%(P<0.01)。结论:PGP和MRP1的表达与白血病疗效及预后之间存在着一定的相关性。     

Impaired telomere regulation mechanism by TRF1 (telomere-binding protein), but not TRF2 expression, in acute leukemia cells

Telomere regulation is suggested to be an important mechanism in cellular proliferation and cellular senescence not only in normal diploid cells but also in neoplastic cells, including human leukemia cells. We studied the possible correlation among telomere length, telomerase (a ribonuclear protein that synthesizes the telemeres de novo) activity, hTERT (a catalytic subunit of telomerase) expression, and TRF1 and TRF2 (telomere DNA binding proteins) expression in human acute leukemia cells. The hTERT expression level was strongly associated with telomerase activity (P=0.0001), indicating that the expression level of the catalytic subunit (hTERT) regulates telomerase activity in human acute leukemia cells. TRF1 expression, which is believed to control telomere length, was significantly elevated in patients with acute lymphoblastic leukemia (ALL) (P=0.0232) compared to those in acute myeloid leukemia (AML); TRF1 expression tended to be higher in patients without telomere shortening (P=0.077) and in those with hTERT expression (P=0.055). This indicates that TRF1 may act to monitor telomere length under the condition of up-regulated telomerase activity in some neoplastic cells. In contrast, TRF2 expression in acute leukemia did not show any correlation with telomere parameters in this study. Although the precise regulation mechanism of telomere length is still uncertain, these results may suggest that regulation of telomere length is partially associated with TRF1 expression, whereas dysfunction of TRF1 expression may be speculated in a subset of acute leukemia.