伴t(16;21)(p11;q22)的恶性血液病的临床和实验分析

目的探讨伴t(16;21)(p11;q22)的恶性血液病的临床及实验室特征。方法骨髓细胞24 h培养后按常规方法制备染色体,用RHG显带技术进行细胞遗传学分析。结果 1例M2的患者其核型分析结果有t(16;21)(p11;q22)的异常,临床和血液学改变符合急性髓细胞白血病-M2a诊断,化疗后未获得完全缓解,中位生存期为6个月。结论 t(16;21)(p11;q22)是一类很独特的白血病亚型有关的易位,为少见的非随机的染色体易位,其临床预后差。     

T(11;18)及核bcl-10蛋白在胃肠MALT淋巴瘤中的表达

为了探讨t(11；18)(q21；q21)染色体易位及核bcl-10蛋白在胃肠粘膜相关淋巴组织淋巴瘤(MALT lymphoma)中的表达，用酸性酚氯仿法从石蜡组织中提取RNA；逆转录合成cDNA后用聚合酶链反应(PCR)扩增API2-MALT1融合基因；用免疫组织化学法检测石蜡切片中bcl—10蛋白的表达。结果表明：42例MALT淋巴瘤中，t(11；18)(q21；q21)染色体易位在低度恶性MALT淋巴瘤中的表达为14％，在伴高恶转化型MALT淋巴瘤中的表达为46％，在40例弥漫大B细胞淋巴瘤(diffuse 1arge B cell lymphoma，DLBCL)对照组中没有表达；43例MALT淋巴瘤中bcl-10蛋白在低度恶性MALT淋巴瘤的核表达为61％，在伴高恶转化型MALT淋巴瘤中的核表达为69％。结论：t(11；18)易位可能与高度进展MALT淋巴瘤有一定相关性，但与DLBCL无关;bcl-10蛋白的核表达在恶性程度不同的两组MALT淋巴瘤中无显著性差异，其原因有待进一步研究。     

慢性粒细胞白血病急变伴t(3;21)(q26;q22)染色体易位受累基因的研究

目的探讨慢性粒细胞白血病（CML）急性髓系白血病（AML）变伴t（3;21）（q26;q22）的受累基因.方法对1例CML AML变伴t（3;21）（q26;q22）患者细胞间期和中期分裂相细胞采用荧光原位杂交技术（FISH）检测AML1和bcr/abl基因重排,RT-PCR联合序列分析检测t（3;21）（q26;q22）受累基因.结果der（3）和der（21）染色体上均检测到AML1基因杂交信号,AML1-MDS1-Evi1、AML1-MDS1、AML1-EAP及Evi1基因均表达,未见AML1-Evi1融合基因表达,AML1-MDS1-Evi1基因表达水平是AML1-MDS1、AML1-EAP表达水平的1.58和1.54倍,患者Evi1基因表达水平是HEL细胞系Evi1表达水平的2.71倍.结论t（3;21）（q26;q22）导致形成AML1-MDS1-Evi1、AML1-MDS1融合基因及Evi1基因激活,这些继发的分子遗传学异常是CML急性变伴t（3;21）（q26;q22）患者急变发生的分子基础.     

8号染色体四体、三体共存的t(15;17)(q22;q12)急性早幼粒细胞白血病

本研究报道首例伴有8号染色体四体(四体8)、8号染色体三体(三体8)异常的t(15；17)急性早幼粒白血病(AML-M3a)，并探讨其形态学、细胞遗传学、分子生物学、免疫学及临床特点。用外周血及骨髓标本直接涂片观察形态学改变；采用骨髓细胞24小时短期培养法制备染色体标本，RHG显带技术进行核型分析；以筑巢式逆转录聚合酶链反应(nested RT—PCR)技术检测PML-RARa融合基因转录本；以间期荧光原位杂交(fluorescence in situ hybridization，FISH)技术检测8号染色体数目异常；以流式细胞术检测免疫表型。结果表明：外周血涂片早幼粒细胞占65％，可见中晚幼粒细胞。骨髓涂片显示有核细胞增生明显活跃，粒系83．6％，其中早幼粒细胞占72．4％，胞浆内可见大量紫红色颗粒。染色体核型分析揭示核型为48，XY， 8， 8，t(15；17)(q22；q12)[16]／47，XY， 8，t(15；17)(q22；q12)[3]／46，XY，t(15；17)(q22；q12)[1]。RT—PCR检测PML-RARa( )。FISH检测显示具有1，2，3，4，5，6个绿色荧光信号细胞的百分比分别为0．5，7，19，55，18和0．5。这不但证实了三体8和四体8克隆的存在．还发现存在一个较小的五体8克隆。白血病细胞免疫表型检测显示CD13(96．2％)、CD33(55．9％)、CYMPO(93．5％)阳性，其余抗原包括淋系抗原在内均为阴性。患者生存期只有10天。结论 本例四体8是t(15；17)的继发性改变，可能是三体8克隆进展的结果。伴有四体8的t(15；17)AML-M3预后差。     

两例急性髓系白血病伴t(6;21;8)(p22;q22;q22)复杂易位患者的临床与实验室研究

目的探讨2例急性髓系白血病（AML）伴t（6;21;8）（p22;q22;q22）复杂易位患者的临床及实验室特点.方法骨髓细胞经短期24 h培养后按常规方法制备染色体标本,R显带进行核型分析;双色双融合AML1/ETO探针进行丝裂间期及中期荧光原位杂交（FISH）检测AML1/ETO融合信号;逆转录-聚合酶链反应（RT-PCR）检测AML1/ETO融合基因转录本;综合分析临床特征.结果2例患者常规细胞遗传学分析显示均存在t（6;21;8）（p22;q22;q22）,间期和中期FISH证实了核型结果;RT-PCR检测到AML1/ETO融合基因转录本;尽管2例患者均诊断为AML-M2,但二者的免疫表型和治疗反应不同.结论t（6;21;8）（p22;q22;q22）是一种少见的t（8;21）（q22;q22）的复杂变异易位,还需要更多的病例以明确其临床特征和预后价值.     

Six families with balanced chromosome translocation associated with reproductive risks in Hainan Province: Case reports and review of the literature

BACKGROUND Balanced translocation refers to the process where breakage and reconnection of chromosomes occur at abnormal positions.As the genetic substance with balanced translocation in individuals does not change,which is usually characterized by normal phenotype and intelligence,the individuals seek medical service after many miscarriages,resulting in considerable mental and physical burdens of the family members.In the current era with rapid advances in detection technology,cytogenetic examination,as a definitive approach,still plays an essential role.CASE SUMMARY We report six cases with balanced chromosome translocation:Case 1:46,XY,t(3;12)(q27;q24.1),infertility after 3 years of marriage;Case 2:46,XX,t(4;16)(q31;q12),small uterus and irregular menstruation;Case 3:46,XY,t(4;5)(q33;q13),9qh+,not pregnant after arrested fetal development;Case 4:46,XX,t(11;17)(q13;p11.2),not pregnant after two times of spontaneous abortion;Case 5:46,XX,t(10;13)(q24;q21.2),not pregnant after arrested fetal development for once;Case 6:46,XX,t(1;4)(p36.1;q31.1),not pregnant after arrested fetal development for two times.The first four cases had chromosomal aberration karyotypes.CONCLUSION These results suggested that balanced chromosomal translocation carriers are associated with reproductive risks and a very high probability of abnormal pregnancy.The discovery of the first four reported chromosomal aberration karyotypes provides an important basis for studying the occurrence of genetic diseases.     

16例伴19p13异常急性淋巴细胞白血病患者的临床和实验室研究

目的 分析伴19p13异常的急性淋巴细胞白血病(ALL)患者的临床和实验室特征:方法 对16例伴19p13异常的ALL患者的细胞形态学、免疫学、细胞遗传学和临床特点进行回顾性分析,并对t(1;19)组和der(19)组的临床和实验室资料进行对比分析.结果 伴19p13异常的ALL占同期ALL的4.02%,其中t(1;19)(q23;p13)15例[平衡易位t(1;19)(q23;p13)8例,不平衡易位der(19)t(1;19)(q23;p13)7例],t(17;19)(q22;p13)1例,t(1;19)组的外周血门细胞汁数和骨髓原始幼稚淋巴细胞比例明显高于der(19)组,而der(19)组的预后较t(1;19)组好.结论 19p13异常是ALL的一个非随机的染色体改变;伴有该异常的ALL患者具有独特的I临床特征和小良预后.     

Interphase cytogenetics for the detection of the t(11;22)(q24;q12) in small round cell tumors.

Among the small round cell tumors differential diagnosis is particularly difficult for their undifferentiated or primitive character. In this mixed group of tumors, only the primitive neuroectodermal tumors, which include Ewing's sarcoma (ES), show the unique and consistent feature of the (11;22)(q24;q12) translocation, which can therefore be considered a hallmark of these neoplasias. We analyzed four primitive neuroectodermal tumor cell lines, one osteosarcoma cell line, and 11 patients by fluorescent in situ hybridization with cosmid clones 23.2 and 5.8, bracketing the t(11;22) at 11q24. Metaphase spreads from tumor cell lines, and from biopsy specimens of three patients with ES were analyzed. In the remaining eight patients comprising five ES, two small cell osteosarcomas and one chronic osteomyelitis, only nuclei preparations were available for analysis. We detected the t(11;22) in interphase nuclei of the four primitive neuroectodermal tumor cell lines, of three patients in which the karyotype demonstrated the translocation and in five cases of ES in which cytogenetic analysis had not been possible. Two cases of small cell osteosarcoma and one chronic osteomyelitis were also analyzed and were both normal with respect to the t(11;22). By analyzing cell lines and small round cell tumor samples by fluorescent in situ hybridization, we established that interphase cytogenetics is a rapid alternative to chromosomal analysis for the detection of the t(11;22) and represents an invaluable tool for the differential diagnosis of small round cell tumors.     

The chromosome translocation (11;14)(p13;q11) associated with T cell acute leukemia. Asymmetric diversification of the translocational junctions

The t(11;14)(p13;q13) translocation associated with T cell acute lymphocytic leukemia generates two abnormal chromosomes, designated 11p+ and 14q-. To investigate the mechanism of t(11;14)(p13;q11) formation, we analyzed the translocation junctions of 11p+ and 14q- from two patients. The 11p+ junctions consisted of precise fusions of a pseudo recombination signal from chromosome 11 and the downstream recombination signal of the TCR D delta 2 gene segment from chromosome 14. In contrast, the 14q- junctions from both patients were diversified by random loss and addition of nucleotides at the translocation site. This asymmetric pattern of junctional diversification is typical of normal Ig/TCR gene rearrangement, and therefore implies that the t(11;14)(p13;q11) translocation arose due to aberrant activity of the Ig/TCR recombinase.     

二例M2型急性髓系白血病染色体t(8;19)(q22;q13)

目的　首次报道 2例M2 型急性髓系白血病 (AML M2 )有染色体t(8;1 9) (q2 2 ;q1 3 )。方法　应用骨髓细胞短期培养法制备染色体标本 ,并应用R和G显带技术进行核型分析 ;例 2 ,应用流式细胞仪和一组单克隆抗体检测其白血病细胞的免疫表型 ,应用筑巢式逆转录 聚合酶链反应 (RT PCR)技术检测其AML1/ETO融合基因转录本。结果　例 1的核型为 4 6,XX ,t(8;1 9) (q2 2 ;q1 3 ) [2 8] / 4 6,XX[2 ] ,例 2的核型为t(8;1 9) (q2 2 ;q1 3 ) ,del(9) (q1 2q2 2 ) [2 3 ] / 4 6,XY[2 ] ;例 2的白血病细胞表达CD13(3 8 8% )、CD33(3 1 8% )、CD34 (80 .9% )和CD19(63 .9% ) ,其AML1/ETO融合基因转录本为阴性。结论　t(8;1 9) (q2 2 ;q1 3 )是t(8;2 1 )的简单变异型 ,其分子学本质有待于进一步研究阐明。     

Simultaneous translocation of both TCR Loci (14q11) with rare partner loci (Xq22 and 12p13) in a case of T-lymphoblastic leukemia

The most common recurrent cytogenetic abnormalities in T-lymphoblastic leukemia (T-acute lymphoblastic leukemia [T-ALL]) involve T-cell receptor (TCR) loci and a variety of partner genes, including HOX11, HOX11L2, MYC, and TAL1. In this report, we present a rare case involving simultaneous translocation of the TCR α/δ loci with different partner loci (Xq22 and 12p13); this resulted in a poor prognosis. Chromosomal analysis showed 46,Y,t(X;14)(q22;q11.2),t(12;14)(p13;q11.2) and FISH analysis by using a T-cell receptor alpha delta DNA probe, Split Signal (DakoCytomation, Denmark), showed translocations at the same TCR α/δ locus on both chromosomes. FISH with 2 bacterial artificial chromosome clones showed break apart signal, which suggests involvement of the IRS4 gene. To our knowledge, this is the first report of T-ALL in which both TCR α/δ loci were translocated with different partner loci, and 1 of the partner loci, Xq22, was a rare translocation partner locus that included IRS4 gene.     

嗜酸性粒细胞增多症的细胞遗传学研究

为探讨染色体异常克隆在嗜酸性粒细胞增多症诊断和鉴别诊断中的意义及克隆性嗜酸性粒细胞增多症涉及的染色体异常,收集了65例嗜酸性粒细胞增多患者的骨髓标本,培养24小时,采用G显带进行核型分析。结果表明：65例中9例拟诊为急性髓细胞性白血病-M4Eo检出特异性的染色体异常inv（16）,而其余的56例以嗜酸性粒细胞增多待诊的患者中5例检出染色体异常克隆,检出率为8.9%。根据临床、血液学资料并结合染色体检出结果,5例患者最后分别被诊断为急性髓系白血病伴嗜酸性粒细胞增多、慢性嗜酸性粒细胞白血病、8p11骨髓增殖综合征、慢性髓系白血病急变、急性髓系白血病-M4Eo。检出的染色体异常克隆分别为＋14、t（5;12）（q31;p13）、t（8;9）（p11;q32）、t（9;22）（q34;q11）和inv（16）（p13q22）。结论：在嗜酸性粒细胞增多症的诊断中,染色体的检测是判定克隆性和诊断慢性嗜酸性粒细胞白血病的重要手段,应作为常规的检测。     

二例伴有dic(9;20)(p11-13;q11)急性淋巴细胞白血病患者的临床和实验研究

目的探讨伴有dic（9;20）（p11-13;q11）的急性淋巴细胞白血病（ALL）的细胞形态学、免疫学、细胞遗传学特征和临床特点.方法骨髓细胞经直接法和24h短期培养后按常规方法制备染色体,采用R显带技术进行细胞遗传学分析.分别以9号和20号染色体着丝粒探针进行双色荧光原位杂交（FISH）检测.结果2例患者的临床和血液学改变符合ALL诊断,免疫表型分析B淋系标志阳性（CD10＋、HLA-DR＋）;染色体核型分析显示2例患者均为dic（9;20）：例1为45,XY,der（9）t（9;20）（p11;q11）,-20[20],例2为45,XX,der（9）t（9;20）（p13;q11）,t（9;22）（q34;q11）,-20[10]/46,idem,＋8[16]/47,idem,＋8,＋21[14];其中1例经双色FISH检测证实9号和20号染色体之间发生了相互易位,且形成双着丝粒染色体.结论dic（9;20）（p11-13;q11）是一种少见的重现性核型异常,可能和ALL有特殊的联系.FISH技术是检测该易位的可靠手段.     

用逆转录－多聚酶链反应监测急性髓系白血病M_（2b）微量残留白血病

急性髓系白血病（ＡＭＬ）Ｍ＿（２ｂ）常伴有ｔ（８：２１）染色体易位，两个染色体重排导致形成ＡＭＬＩ／ＭＴＧ８融合基因，并持续产生融合基因转录本。作者利用逆转录。多聚酶链反应（ＲＴ－ＰＣＲ）扩增ＡＭＬ１／ＭＴＧ８融合基因转录本进行ＡＭＬ－Ｍ＿（２ｂ）微量残留白血病的监测，在１３例完全缓解的患者中，１２例可检出残留白血病细胞。经随诊这１２例中，２例已复发，１例死于强化治疗骨髓抑制期，９例仍持续完全缓解。