流式细胞术相关性分析急性髓系白血病p21（H—ras）与DHA倍体

用流式免疫法分析３０例初治急性髓系白血病细胞ｒａｓ癌基因产物ｐ２１蛋白和ＤＮＡ倍体的关系。发ｐ２１表达阴性者１７例，阳性者１３例。Ｐ２１阳性者骨髓与外周血原始细胞百分比较高，外周白细胞数较低。     

卵巢癌ras癌基因产物p21的定量分析

目的：探讨卵巢癌ｒａｓｐ２１表达与ＤＮＡ倍体水平及临床病理参数的关系。方法：采用流式免疫荧光技术。结果：３６例卵巢癌１４例ｒａｓｐ２１呈阳性表达，ｒａｓｐ２１阳性表达与组织分级无关：ｒａｓｐ２１阳性表达量在二倍体与异倍体之间有显著性差异；ｒａｓｐ２１阳性表达多见于粘液性卵巢癌。结论：ｒａｓｐ２１表达量与ＤＮＡ倍体相关     

定量研究乳腺癌ras癌基因产物p21的表达

应用流式细胞术和细胞免疫荧光染色技术，对４３例乳腺癌的癌基因ｒａｓｐ２１的表达进行了定量研究。并探讨了与ＤＮＡ倍体和细胞增殖活性之间的关系。结果表明，乳腺癌ＤＮＡ倍体出现率和ＤＩ值均随肿瘤的恶性程度增高而增高。ｒａｓｐ２１的表达结果显示，肿瘤的分化程度与ｒａｓｐ２１的表达密切相关。ｐ２１表达阳性率随组织学分级而增高，Ⅰ级ｐ２１￣＋为４４．４％（４／９例），Ⅱ级ｐ２１￣＋为８７．５％（１４／１６例），Ⅲ级ｐ２１￣＋９４．４％（１７／１８例）．并发现乳腺癌倍体和细胞增殖活性与ｒａｓｐ２１的表达密切相关，异倍体肿瘤ｐ２１￣＋表达明显高于二倍体肿瘤，而ｒａｓｐ２１表达阳性的乳腺癌，其增殖指数值明显高于ｐ２１表达阴性的乳腺癌。     

胃癌及胃粘膜非典型增生组织p21ras表达与DNA倍体关系的探讨

用免疫组化和自动图像分析方法检测２７例胃癌、２２例非典型增生和９例正常胃粘膜组织中ｐ２１ｒａｓ表达及ＤＮＡ倍体分布类型，发现胃粘膜非典型增生组织中ｐ２１ｒａｓ阳性率最高。２７例胃癌组织中，ＤＮＡ倍体分布类型属Ⅰ型、Ⅱ型及Ⅲ型的ｐ２１ｒａｓ阳性率分别为８３．３％、６６．７％及３３．３％。表明胃癌组织ｐ２１ｒａｓ表达水平随ＤＮＡ含量不断增多，随倍体成倍增加而逐渐下降，明显低于非典型增生组织，提示ｐ２１ｒａｓ过度表达主要出现在细胞表型发生明显转化之前。     

子宫内膜癌ras癌基因产物p21和DNA倍体的研究

为了观察ｒａｓ癌基因产物ｒａｓｐ２１在子宫内膜癌及癌前病变组织中的表达，及ｒａｓｐ２１与ＤＮＡ倍体的关系，应用流式细胞术和细胞免疫荧光技术检测了３２例子宫内膜癌、２６例癌前病变和１０例正常内膜组织中的ｒａｓｐ２１的表达情况。结果为正常内膜组织中ｒａｓｐ２１表达阴性，子宫内膜癌ｒａｓｐ２１的表达高于癌前病变。ｒａｓｐ２１表达的荧光指数随子宫内膜癌组织学分级的升高而增加，但与临床分期、肌层浸润和淋巴结转移无关。ＤＮＡ倍体与ｒａｓｐ２１的表达量有关。表明ｒａｓｐ２１在子宫内膜癌和癌前病变有较高的表达，这可能与子宫内膜癌的发生有关。检测ｐ２１蛋白和ＤＮＡ倍体有助于判断肿瘤的恶性程度和预后。     

ras基因的表达与胃癌细胞生物学特性的相关研究

为研究ｒａｓ基因在胃癌中的表达，采用组织化学、免疫化学和自动图像分析方法，检测了５４例胃癌切除标本的ｒａｓ基因表达、癌细胞核形态参数和ＤＮＡ含量及倍体分布类型。发现胃癌细胞ｐ２１表达水平随着ＤＮＡ含量不断增多、倍体成倍增加而逐渐下降。表明ｒａｓ过度表达主要出现在细胞表型发生明显转化之前。此外，发现胃癌细胞ｐ２１的表达水平与癌细胞核形态参数、癌肿大小、有无淋巴结转移均无关。     

膀胱移行细胞癌细胞DNA含量,rasp21和p53蛋白表达的综合定量研究

目的：探讨细胞ＤＮＡ含量、抑癌基因ｐ５３和癌基因ｒａｓ表达在膀胱移行细胞癌发生发展中的综合作用及其与临床病理特征的关系。方法：以免疫流式细胞光度术与病理形态学相结合的方法对５６例膀胱移行细胞癌细胞ＤＮＡ含量、ｒａｓｐ２１和ｐ５３蛋白表达进行了定量研究。结果：研究发现，本组膀胱移行细胞癌不管从Ｓ％、ＰＩ还是ＤＩ均明显高于正常膀胱粘膜上皮，其平均ＤＩ已处于ＤＮＡ异倍体范围。癌基因ｒａｓｐ２１的阳性表达及抑癌基因ｐ５３的异常表达率分别为６２．５％和７６．７％。随膀胱移行细胞癌分化程度的降低，肿瘤细胞增殖活性（Ｓ％、ＰＩ）和ＤＮＡ含量及ＤＮＡ异倍体出现率均增高，Ⅲ级组上述参数明显高于Ⅰ、Ⅱ级组和对照组（Ｐ分别＜０．０１，０．０２和０．０１）。ｒａｓｐ２１和ｐ５３表达的阳性率随分化程度的降低而明显增高，Ⅲ级病例ｐ５３的阳性表达率达１００％，ｒａｓｐ２１的阳性表达率亦达８０％，且其表达强度亦高于Ⅰ／Ⅱ级组。此外，分化越低，ｒａｓｐ２１＋／ｐ５３＋和ｒａｓｐ２１＋／ｐ５３＋／ＤＮＡ异倍体病例亦越多（Ｐ＜０．０５）。结论：膀胱移行细胞癌的发生发展是多种因素协同作用的结果，从遗传物质ＤＮＡ到癌基因ｒａｓ家族和抑癌基因ｐ５３在     

子宫内膜癌和子宫颈癌p21与DNA倍体的研究

目的研究ｒａｓｐ２１致癌基因和ＤＮＡ倍体与子宫颈癌及子宫内膜癌的关系。方法应用细胞免疫荧光技术和流式细胞术对４０例宫颈癌、２０例慢性宫颈炎、３２例子宫内膜癌和１３例癌前病变进行了ｒａｓｐ２１致癌基因的表达量及ＤＮＡ倍体的测定。结果子宫颈癌和子宫内膜癌ｒａｓｐ２１的表达量高于慢性宫颈炎和子宫内膜癌前病变,并与二者的组织学分级有关。ＤＮＡ倍体与ｒａｓｐ２１的表达量有关。结论ｒａｓｐ２１的表达与子宫颈癌和子宫内膜癌的发生有关。检测ｐ２１蛋白和ＤＮＡ倍体有助于判断这两种肿瘤的恶性程度和预后,并应积极治疗慢性宫颈炎     

子宫内膜癌和子中颈癌p21与DNA倍体的研究

目的 研究ｒａｓ ｐ２１致癌基因和ＤＮＡ倍体与子宫颈癌及子宫内莫吕的关系。方法 应用细胞免疫灾光技术和流式细胞术对４０例审颈癌、２０例慢性宫颈炎、３２ 子宫内膜癌和１３例癌前病变进行了ｒａｓ ｐ２１致癌基因的表达量及ＤＮＡ倍体的测定。结果子宫颈癌和子宫内膜癌ｒａｓ ｐ２１的表达量有关。结论ｒａｓ ｐ２１的表达与子宫颈癌和子宫内膜癌的发生有关。检测ｐ２１蛋白和ＤＮＡ倍体体有助于判断这两种肿瘤的恶性     

胃癌细胞DNA含量和rasp21表达的预后意义

目的主要探讨ｒａｓｐ２１表达和ＤＮＡ含量测定的预后意义。方法采用流式细胞术对４１例进展期胃癌的石蜡包埋标本进行了ｒａｓｐ２１表达和ＤＮＡ含量的定量检测。结果ＤＮＡ二倍体组的５年生存率（３５．７％）较异倍体组高（２２．２％，Ｐ＜０．０５），ｒａｓｐ２１低表达组（Ｆｉ≤Ｘ）的５年生存率（２９．１％）较ｒａｓｐ２１高表达组（Ｆｉ＞Ｘ）的５年生存率（１４．３％）高（Ｐ＜０．０５）；高ｒａｓｐ２１表达异倍体胃癌（５年生存率１４．４％）较低ｒａｓｐ２１表达异倍体胃癌（５年生存率２８．６％）预后不良（Ｐ＜０．０５）。结论ＤＮＡ倍体类型和ｒａｓｐ２１表达，尤其是双参数同步分析，可望成为评估胃癌预后的客观指标之一。     

Frequent expression of MDR1 and MDR3 genes in acute myelocytic leukemia cells with t(8;21) (q22;q22)

Multidrug resistance (MDR) 1 and MDR3 gene expression were examined in acute myelocytic leukemia (AML) cells from 126 Japanese patients. In 119 AML patients at diagnosis 52 were revealed to have P-gp/MDR1 (43.7%). AML cases with t(8;21) had a higher incidence of P-gp expression (13/17; 76.5%) than cases with other karyotypes (33/89; 37.1%) (p=0.0062). CD19(+) cases expressed P-gp frequently (17/25) as did CD7(+) cases (24/35). In 17 CD19(+) AML with P-gp expression, 12 had t(8;21) abnormality. In 68 AML samples examined, MDR3 mRNA was detected in 11 cases, 9 of which had the t(8;21) abnormality. The MDR3(+) t(8;21) AML samples were also positive for CD19. We analyzed P-gp expression at both diagnosis and relapse in 18 AML patients. All 11 P-gp(+) cases at relapse, in which 5 patients were P-gp negative at diagnosis, showed either t(8;21) or CD7 positivity. Our data demonstrated that expression of MDR1 and MDR3 in AML is closely associated with chromosome abnormality t(8;21) and expression of immature lymphoid antigen CD19 as well as CD7. Kasumi-1, a t(8;21) AML cell line, was demonstrated to lose P-gp by the treatment of 1,25(OH)(2)D-3, a monocyte/macropharge differentiation inducer, suggesting the possible contribution to the therapy for AML.     

伴有6号染色体长臂缺失的急性髓细胞白血病二例报告及文献复习

 目的　了解6q-异常急性髓细胞白血病（AML）的临床和生物学特点。方法　报道2例伴有6号染色体长臂缺失(6q-)的AML,并对伴有6q-异常AML的有关文献进行复习。结果　2例患者分别诊断为AML-M1和AML-M2,均表达髓系抗原,不表达淋巴细胞抗原。染色体核型分别为：46,XX, del(6)(q21q25),t(4;7)(q10;q10)[3]/46,XX,del(6)(q21q25)[2]/46,XX[25]以及46,XX,del(6)(q23),t(7;11)(p15;p15)[5]/46,XX,t(7;11)(p15;p15)[9]/46,XX[6]。现有文献共报道了伴有6q-异常AML 28例（包括该组报道的2例）。大部分患者伴有附加染色体异常。6q-的断裂点广泛分布于q12-q27,但主要累及6q21-q23区域。总体看来,伴有6q-异常的AML对化疗效果差、生存期短。6q-异常克隆本身可能导致了AML的临床恶性过程。AML患者出现6q-,可能与6号染色体长臂上myb以外癌基因的激活或抗癌基因的丢失有关。结论　AML伴有6q-异常很少见,具有自身的生物学特点,临床预后不良。     

Fluorescence in situ Hybridization Analysis of 12;21 Translocation in Japanese Childhood Acute Lymphoblastic Leukemia

Fluorescence in situ hybridization (FISH) analysis was applied to detect t(12;21) using two yeast artificial chromosome probes and cosmid probes covering the TEL(ETV6) and the AML1 gene to clarify the incidence of abnormality of t(12;21) in Japanese childhood acute lymphoblastic leukemia (ALL). We detected seven TEL/AML1 fusion positive patients (9.5%), all of whom were diagnosed as B-lineage ALL, among 74 childhood ALL. On the other hand, no TEL/AML1 fusion positive patients were found among 37 adult ALL. The incidence among Japanese seemed to be lower than that among other nations. Of the seven patients with the TEL/AML1 fusion, five exhibited normal karyotype, one was t(8;12)(q11;p13), i(21q) and the remaining one exhibited a near-triploid karyotype in conventional G-banding. The FISH method clearly demonstrated that all patients with the TEL/AML1 fusion had subpopulations of leukemic cells with deletion of the normal TEL allele, which is significant for understanding the progression of leukemia with t(12;21).     

急性白血病p27基因表达的临床意义

 目的　探讨急性白血病（AL）p27基因mRNA的表达及临床意义。方法　采用RT-PCR检测65例初治AL和41例造血系统非恶性肿瘤患者（对照组）的骨髓单个核细胞中p27 基因mRNA的表达水平,分析p27 mRNA表达与AL的年龄、性别、外周血白细胞计数和髓外浸润临床特征的相关性。结果　AL中p27基因mRNA表达的阳性率为36.9 %（24／65）,显著低于对照组的87.8 %（36／41）,差异有统计学意义（P＜0.05）,急性髓细胞白血病（AML）组和急性淋巴细胞白血病（ALL）组分别为34.2 %（13／38）和37.5 %（9／24）,均低于对照组,差异有统计学意义（均P＜0.05）,但AML组和ALL组比较,差异无统计学意义（P＞0.05）。年龄≥14岁组（52例）和＜14岁组（13例）比较,p27 mRNA表达差异无统计学意义（P＞0.05）,男性组（34例）和女性组（31例）比较,差异无统计学意义（P＞0.05）,外周血白细胞计数≥20×109／L组（31例）和＜20×109／L组（34例）比较,与白细胞计数呈负相关（r＝-0.284,P＜0.05）,有髓外浸润组（37例）和无髓外浸润组（28例）比较,与髓外浸润呈负相关（r＝-0.300,P＜0.05）。结论　AL存在p27基因 mRNA的表达缺失,缺失同时存在于AML和ALL中,缺失与患者外周血白细胞计数、髓外浸润呈负相关,这可能是AL发生、发展的机制之一。     

Expression of the myeloperoxidase gene in AC133 positive leukemia cells relates to the prognosis of acute myeloid leukemia

We previously reported that the percentage of myeloperoxidase (MPO) positive blasts had a prognostic impact on survival of patients with acute myeloid leukemia (AML). To extend this observation, we quantitatively measured the level of the MPO gene in AC133 positive leukemia cells that would contain a putative AML stem/progenitor compartment. AML cases were divided into the MPO gene high (MPOg-H) and MPO gene low (MPOg-L) groups. Only patients belonging to the MPOg-H group had a favorable chromosomal translocation, t(8;21), and having no morphological dysplasia that was associated with MPOg-L. The difference in the survival of MPOg-H and MPOg-L was statistically meaningful, demonstrating the possible prognostic impact of the expression of MPO gene in AC133 positive leukemia cells.     

Incidence and relevance of secondary chromosome abnormalities in childhood TEL/AML1+ acute lymphoblastic leukemia: an interphase FISH analysis.

The aim of the present study was to determine the frequency and clinical relevance of the most common secondary karyotype abnormalities in TEL/AML1+ B-cell precursor acute lymphoblastic leukemia (ALL) as assessed with fluorescence in situ hybridization (FISH) analyses. Screening of 372 patients who were enrolled in two consecutive Austrian childhood ALL multicenter trials identified 94 (25%) TEL/AML1+ cases. TEL deletions, trisomy 21 and an additional der(21)t(12;21) were detected in 52 (55%), 13 (14%) and 14 (15%) TEL/AML1+ patients, respectively. The 12p aberrations (P=0.001) and near tetraploidy (P=0.045) were more common in TEL/AML1+ patients, whereas the incidence of diploidy, pseudodiploidy, hypodiploidy, low hyperdiploidy, near triploidy, del(6q), chromosome 9 and 11q23 abnormalities was similar among TEL/AML1+ and TEL/AML1- patients. None of the TEL/AML1+ patients had a high hyperdiploid karyotype. Univariate analysis indicated that among TEL/AML1+ patients those with a deletion of the nontranslocated TEL allele had a worse prognosis than those without this abnormality (P=0.034). We concluded that the type and incidence of the most common secondary aberrations in TEL/AML1+ ALL can be conveniently identified with little additional effort during interphase screening with appropriate TEL and AML1 FISH probes. We also provided preliminary evidence that the deletion of the nontranslocated TEL allele may adversely influence the clinical course of TEL/AML1+ ALL.     

Incidence of MLL rearrangement in acute myeloid leukemia, and a CALM-AF10 fusion in M4 type acute myeloblastic leukemia

To determine the incidence of the mixed lineage leukemia (MLL) gene rearrangements in acute myeloid leukemia (AML) without cytogenetically-detected 11q23 abnormalities, we screened 64 cases of AML at diagnosis for MLL rearrangement by FISH. Three cases (4.7%) had a MLL rearrangement detected; one was shown to have a cryptic t(11;22)(q23;q11) and another to have a t(9;11)(p21-22;q23) which had been missed by the conventional cytogenetic study. No 11q23 structural abnormality was visible in the third case. Twenty-six of the 64 cases were further studied by Southern blotting and DNA hybridization, and four of these cases (15%) were found to have MLL rearrangement: in three of these, FISH had not detected any abnormality. FISH was also used to confirm MLL involvement in eight cases of AML that had a cytogenetic abnormality at 11q23; in one of these, Southern blot did not show a rearrangement. The survival of patients with MLL abnormalities identified by cytogenetics, FISH and/or DNA analysis was significantly worse than that of patients without MLL abnormalities (event-free survival p = 0.016) although two patients with a t(9;11)(p21-22;q23) were long-term survivors, consistent with this particular translocation having a better prognosis. One further case with a cytogenetic abnormality close to 11q23 was studied; it was found to have a t(10;11)(p13;q21), and the breakpoints were shown by FISH to involve the Clathrin Assembly Lymphoid Myeloid (CALM) gene at 11q21 and the AF10 gene at 10p13. Our data confirm the value of combining cytogenetic, FISH and molecular analyses to define the incidence and precise nature of MLL and 11q23 abnormalities in AML.     

11例t(16;21)(p11;q22)急性髓系白血病病例报告并文献复习

目的:探讨11例伴t(16;21)(p11;q22)染色体易位的急性髓系白血病（acute myeloid leukemia,AML)患者的临床和实验室特点。方法:回顾性分析2007年07月至2022年03月我院收治的11例t((16;21)(p11;q22)染色体易位的AML患者临床及实验室特征并复习相关文献。结果:11例t(16;21)(p11;q22)染色体易位的白血病均为AML,FAB分型:M2型4例,M4型1例,M5型3例,AML(非M3)型3例;其中男5例,女6例。染色体R显带分析11例均可见到t(16;21)(p11;q22)染色体易位,其中9例伴有附加染色体异常。融合基因TLS/FUS-ERG检测了9例均为阳性。免疫表型除表达髓系CD34、CD117、CD33、CD13、CD38外,均表达CD56。化疗1个周期后完全缓解7例。结论:t(16;21)(p11;q22)染色体易位是一种少见的重现性染色体异常,该易位产生TLS/FUS-ERG融合基因,免疫学检测多伴CD56阳性,以AML中M2/M5型多见,化疗1个周期大部分可完全缓解,但短期内易复发,预后不良。