共查询到20条相似文献,搜索用时 203 毫秒
1.
急性早幼粒细胞白血病PML/RARα异型的临床意义 总被引:3,自引:1,他引:3
为评价急性早幼粒细胞白血病(APL)PML/RARα异型与临床治疗及预后的相关性,对7l例诱导治疗的APL患者定期进行血像、骨髓像检查,用巢式RT—PCR检测PML/RARα不同转录本。结果表明:短型(s)和V型白细胞总数比长型(L型)显著升高,所以较易早期发生严重的出血合并症。S型和V型PML/RARα患者的复发率高于L型患者。结论:APL患者PML/RARα异型可作为独立的预后因素。 相似文献
2.
为了探讨双色荧光原位杂交(D—FISH)技术在骨髓涂片(BMS)上检测PML/RARα基因重排对急性早幼粒细胞白血病(APL)的诊断价值,采用光谱绿(Spectrum Green)和光谱桔红(Spectrum Orange)分别标记PML和RARα两种基因探针对27例临床拟诊为APL的患者进行BMS-D—FISH检测,并与常规细胞遗传学(CCG)、逆转录-聚合酶链反应(RT—PCR)检测结果作比较。结果表明:18例初诊患者中,CCG检出t(15;17)者14例,他们的BMS-D-FISH和RT—PCR均证实有PML/RARα基因重排,从而肯定了对APL的诊断;而CCG未检见t(15;17)易位的4例中有1例显示阳性的BMS-D-FISH和RT—PCR结果,证实该例有隐匿易位存在,其余3例的两种检测均是阴性,因而他们被重新诊断为AML而不是APL;9例缓解患者中,CCG查出1例部分缓解患者有t(15;17)易位,其BMS-D—FISH和RT—PCR均为阳性,而8例完全缓解患者(6例伴正常核型,2例未作CCG检测)的BMS-D-FISH和RTPCR检测显示6例阴性,2例阳性,提示该2例患者有微小残留病(MRD)存在。结论:BMS—D—FISH是检测APLPML/RARα基因重排的敏感可靠方法,有助于APL确诊及其MRD检测,适合于CCG检测失败、伴有隐匿易位、RT—PCR检测缺乏材料以及需作回顾性研究者。 相似文献
3.
<正>急性早幼粒细胞白血病(APL)是急性粒细胞白血病的一种亚型,其特征是15号染色体上的早幼粒细胞白血病基因(PML)与17号染色体上的维甲酸受体α基因(RARα)发生易位。该融合基因的转录导致PML/RARα融合蛋白通过与RAR元素的相互作用阻断参与骨髓细胞分化的关键基因的表达。PML/RARα融合蛋白抑制PML和RARα的正常功能,抑制细胞凋亡[1]。临床上APL发病常较为凶险,早期弥散性血管内凝血(DIC)死亡率高, 相似文献
4.
5.
PML-RARα及RARα融合蛋白在三硫化二砷诱导的NB4细胞凋亡中的作用研究 总被引:8,自引:0,他引:8
为研究PML-RARα及RARα融合蛋白在三硫化二砷(As2S3)诱导的人早幼粒细胞白血病细胞系NB4细胞凋亡中的作用,本研究应用细胞形态观察、流式细胞术测定及DNA电泳等方法观察三硫化二砷对NB4细胞的诱导凋亡作用,用染色体G显带技术、反转录PCR及Western印迹测定这一过程中PML-RARα融合基因及其表达产物、野生型RARα蛋白的变化。结果表明,三硫化二砷在0.5-2μmol/L之间能诱导NB4细胞凋亡,在此过程中PML-RARα融合基因无明显变化,但PML-RARα融合蛋白和野生型RARα蛋白明显减少。结论提示PML-RARα融合蛋白和野生型RARα蛋白的降解在三硫化二砷诱导的NB4细胞凋亡过程中可能起了重要作用。 相似文献
6.
急性早幼粒细胞白血病PML/RARα融合基因检测及临床意义 总被引:1,自引:0,他引:1
急性早幼粒细胞性白血病(APL)是一组累及 17号染色体上的维甲酸受体α基因,其中t(15;17)(q22;q21)易位后形成的早幼粒细胞性白血病(PML)/维甲酸受体α(RARα)融合基因在APL中的重视率最高,占90%以上[1].本研究以34例形态学诊断为APL患者和2例疑似APL患者为对象,采用筑巢式逆转录聚合酶链反应(RT-PCR)方法检测患者PML/RARα融合基因,并追踪观察部分患者PML/RARα融合基因的动态变化,探讨其在诊断、疗效评估及预测预后中的意义. 相似文献
7.
8.
目前认为急性早幼粒细胞白血病(APL )属于急性髓细胞白血病(AML )的特殊类型[1],由于 APL 细胞存在 t (15;17)(q22;q21),该易位使第15号染色体长臂2区2带的早幼粒细胞白血病基因(PML)和第17号染色体长臂2区1带的维甲酸受体‐α(RARα)基因形成 PML /RARα融合基因,该基因在产生过程中因断裂点不同及 mRNA 的剪切、拼接不同会产生不同的异构体并在 APL 发病中起到重要作用[2]。本院收治2例APL 患儿出现新的 PML /RARα融合基因变异体,现报道如下。 相似文献
9.
同时具有染色体t(8;21)和t(15;17)的急性白血病一例 总被引:2,自引:0,他引:2
目的 报道1例同时具有t(8;21)和t(15;17)的染色体复杂异常的急性髓系白血病(AML)。方法 骨髓细胞经过24h培养,按常规方法制备染色体标本,用R显带技术进行核型分析。以RT-PCR方法检测AML1/ETO、PML-RARα融合基因。结果 染色体核型分析结果为45,X,-X,t(8;21),t(15;17)。RT-PCR方法检测发现AML1/ETO及PML-RARα融合基因转录本。结论 同时具有t(8;21)和t(15;17)的AML菜可能为一新的临床遗传学类型。 相似文献
10.
赵峻峰 《国外医学:输血及血液学分册》2005,28(5):391-394
实时定量逆转录聚合酶链反应是目前最精确地检测急性白血病微小残留病的方法,对急性早幼粒细胞PML/RARα融合基因表达量的测定及动态变化监测,取得PML/RARα融合基因的表达拷贝数,对临床治疗、预防复发、延长患者生存期,最终治愈白血病具有重要的指导意义。 相似文献
11.
12.
急性早幼粒细胞白血病基因分析 总被引:3,自引:0,他引:3
目的:分析急性早幼粒细胞白血病(APL)患者经全反式维甲酸(ATRA)联合细胞毒药物及异基因骨髓移植(alo-BMT)治疗后融合基因的变化。方法:采用逆转录-多聚酶链反应(RT-PCR)对22例APL患者治疗前后RARα/PML融合基因进行检测。其中12例患者为单纯化疗,10例接受了alo-BMT,9例患者于第1次完全缓解(CR1)期、1例于第1次复发(RR1)期接受了alo-BMT。结果:单纯维甲酸诱导完全缓解时,75%APL患者融合基因仍然阳性;继用强化疗后83%患者融合基因转为阴性,RT-PCR转阴时间为发病后1~39个月;alo-BMT后4个月内及4个月后,分别有62.5%及85.7%患者融合基因转阴。结论:化疗及BMT均可使患者融合基因转阴,alo-BMT似乎能更快地清除体内白血病细胞 相似文献
13.
T R Randolph 《Clinical laboratory science》2000,13(2):106-116
OBJECTIVES: To identify the chromosomal translocation common in M3 and discuss its diagnostic use to: Compare acute leukemia with chronic leukemia and other forms of cancer. Describe the molecular defect including the fusion gene and fusion protein produced from the translocation. Discuss the proposed mechanism of leukemogenesis in M3. Discuss the proposed mechanism of differentiation induction stimulated by ATRA therapy. Present the future direction of this and other forms of therapy. DATA SOURCES: Current literature. DATA SYNTHESIS: Acute promyelocytic leukemia (AML-M3) is a form of acute leukemia that presents with a less dramatic leukocytosis, anemia, and thrombocytopenia than other acute leukemias. However, AML-M3 has a lower first remission rate and a higher morbidity and mortality rate than most of the other acute leukemias when treated with conventional chemotherapy. AML-M3 frequently stimulates a serious concomitant coagulation disorder, disseminated intravascular coagulation, which is a major contributor to the high mortality rate. This and other devastating sequela of M3 have prompted clinicians and investigators to develop methods of improving diagnosis and therapy. In 1977 the method of diagnosis confirmation was improved by the identification of a consistent chromosomal translocation involving the long arms of chromosomes 15 and 17. Identification of the specific molecular lesion that produced the t(15;17) translocation occurred in 1990 and was shown to involve the retinoic acid receptor alpha gene (RAR alpha). Because the RAR alpha gene is mutated in all AML-M3 patients studied so far and because it is often the only mutation identified, several proposed mechanisms of leukemogenesis have evolved. From these discoveries a novel approach to cancer treatment focusing on differentiation therapy instead of traditional chemotherapy emerged. All-trans retinoic acid (ATRA) has been shown to stimulate differentiation of promyelocytes from the malignant clone and has become an important element in the treatment of patients with AML-M3. CONCLUSION: Since the discovery of the t(15;17) translocation, the identification of the fusion gene containing the retinoic acid receptor alpha, and the success of ATRA as a form of differentiation therapy, the diagnosis and treatment of AML-M3 has dramatically improved. In addition, AML-M3 has become a model system used to study the mechanisms that produce uncontrolled growth and lack of differentiation in leukemic cells (leukemogenesis) and the mechanisms of therapeutic reversal of this block in differentiation (differentiation therapy). 相似文献
14.
H Rennert T Golde R B Wilson S L Spitalnik V M Van Deerlin D G Leonard 《Molecular diagnosis》1999,4(3):195-209
15.
目的 探讨白血病患者GATA-2基因的表达及其临床意义。方法 应用RT-PCR对各类白血病患者GATA-2的表达进行检测,慢性粒细胞白血病(CML)和急性早幼粒细胞白血病(APL)同时检测bcr/abl和PML/RARα的表达。结果 初治/复发的急性髓系白血病(AML)和急性淋巴细胞白血病(ALL)GATA-2的阳性率分别为93%和70%,慢性粒细胞白血病慢性期(CML-CP)为83%。正常人骨髓和外周血未检测到GATA-2。缓解期AML患者GATA-2的表达与初治/复发AML相比,差异无显著性;移植治疗后患者GATA-2的表达率显著下降;移植治疗后的CML患者在bcr/abl转阴后仍可检出GATA-2,而移植治疗后APL患者PML/RARα和GATA-2都为阴性。结论 GATA-2基因转录产物在正常人骨髓和外周血中低表达,在各类白血病中高表达。缓解期骨髓中仍有GATA-2的高表达,移植治疗后GATA-2表达显著下降。GATA-2高表达反映了患者体内残存的白血病干细胞,自体或异基因骨髓移植可以更好地清除白血病干细胞。 相似文献
16.
Rearrangements of the retinoic acid receptor alpha and promyelocytic leukemia zinc finger genes resulting from t(11;17)(q23;q21) in a patient with acute promyelocytic leukemia. 总被引:13,自引:0,他引:13
下载免费PDF全文
![点击此处可从《The Journal of clinical investigation》网站下载免费的PDF全文](/ch/ext_images/free.gif)
S J Chen A Zelent J H Tong H Q Yu Z Y Wang J Derr R Berger S Waxman Z Chen 《The Journal of clinical investigation》1993,91(5):2260-2267
Cytogenetic study of a patient with acute promyelocytic leukemia (APL) showed an unusual karyotype 46,xy,t(11;17) (q23;21) without apparent rearrangement of chromosome 15. Molecular studies showed rearrangements of the retinoic acid receptor alpha (RAR alpha) gene but no rearrangement of the promyelocytic leukemia gene consistent with the cytogenetic data. Similar to t(15;17) APL, all-trans retinoic acid treatment in this patient produced an early leukocytosis which was followed by a myeloid maturation, but the patient died too early to achieve remission. Further molecular analysis of this patient showed a rearrangement between the RAR alpha gene and a newly discovered zinc finger gene named PLZF (promyelocytic leukemia zinc finger). The fusion PLZF-RAR alpha gene found in this case, was not found in DNA obtained from the bone marrow of normals, APL with t(15;17) and in one patient with AML-M2 with a t(11;17). Fluorescence in situ hybridization using a PLZF specific probe localized the PLZF gene to chromosomal band 11q23.1. Partial exon/intron structure of the PLZF gene flanking the break point on chromosome 11 was also established and the breakpoint within the RAR alpha gene was mapped approximately 2 kb downstream of the exon encoding the 5' untranslated region and the unique A2 domain of the RAR alpha 2 isoform. 相似文献
17.
18.
Jacqueline E. Payton Nicole R. Grieselhuber Li-Wei Chang Mark Murakami Gary K. Geiss Daniel C. Link Rakesh Nagarajan Mark A. Watson Timothy J. Ley 《The Journal of clinical investigation》2009,119(6):1714-1726
Acute promyelocytic leukemia (APL) is characterized by the t(15;17) chromosomal translocation, which results in fusion of the retinoic acid receptor α (RARA) gene to another gene, most commonly promyelocytic leukemia (PML). The resulting fusion protein, PML-RARA, initiates APL, which is a subtype (M3) of acute myeloid leukemia (AML). In this report, we identify a gene expression signature that is specific to M3 samples; it was not found in other AML subtypes and did not simply represent the normal gene expression pattern of primary promyelocytes. To validate this signature for a large number of genes, we tested a recently developed high throughput digital technology (NanoString nCounter). Nearly all of the genes tested demonstrated highly significant concordance with our microarray data (P < 0.05). The validated gene signature reliably identified M3 samples in 2 other AML datasets, and the validated genes were substantially enriched in our mouse model of APL, but not in a cell line that inducibly expressed PML-RARA. These results demonstrate that nCounter is a highly reproducible, customizable system for mRNA quantification using limited amounts of clinical material, which provides a valuable tool for biomarker measurement in low-abundance patient samples. 相似文献
19.
20.
白血病基因产物靶向治疗的基础和临床研究 总被引:5,自引:4,他引:5
全反式维甲酸(ATRA)和三氧化二砷(As2O3)治疗急性早幼粒细胞性白血病(APL)获得了很大成功,已经成为白血病靶向治疗研究的代表性模式ATRA与As2O3的作用靶点均为异常转录因子PML—RARα,前者通过针对RARα,而后者通过PML SUMO化后使PML—RARα致病蛋白降解,导致APL细胞分化和凋亡。ATRA与As2O3联合治疗初发APL,证实了两药的相互协同作用,获得了迄今为止成人急性白血病治疗的最好疗效。酪氨酸激酶抑制剂格力维(Gleevec)在慢性粒细胞白血病(CML)治疗中获得了成功。联合应用格力维与砷剂治疗CML已在临床和实验中初步证实其有效性,这一治疗方案是基于针对ABL异常的酪氨酸激酶活性与降解BCR—ABL融合蛋白的双重靶向作用。白血病多靶点联合治疗的思路将进一步拓展至ANLL-M2b型白血病,为该类白血病提供新的治疗方案,有可能使该类白血病获得更为有效的治疗效果。 相似文献