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.     

Evidence by spectral karyotyping that 8q11.2 is nonrandomly involved in lipoblastoma

We report two cases of lipoblastoma with chromosome 8-related aberrations, ie, a 92,XXYY,t(7;8)(p22;q11.2)x2 [8]/46,XY[16] in Case 1 and a 46,XY,−8,−13,add(16)(q22),+mar, +r [cp13]/46,XY[7] in Case 2. Using spectral karyotyping and fluorescence in situ hybridization techniques, the karyotype of Case 2 was redesignated as 46,XY, r(8), del(13)(q12), der(16)ins(16;8)(q22;q24q11.2)[cp13]/46,XY[7]. This report delineates a new chromosome rearrangement, ie, der(16)ins(16;8)(q22;q24q11.2) in lipoblastoma, and also confirms the t(7;8)(p22;q11.2), reported only once previously, as a recurrent translocation involved in such a tumor. These findings provide valuable information for clinical molecular cytogenetic diagnosis of lipoblastoma. Furthermore, this report highlights the value of cytogenetic and molecular cytogenetic analysis in differential diagnosis of childhood adipose tissue tumors and adds to the number of lipoblastomas reported with chromosomal abnormalities at 8q11.2.     

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.     

间期荧光原位杂交技术检测急性粒-单核细胞白血病inv(16)

目的 探讨荧光原位杂交（FISH）技术在检测inv(16)(p13q22)中的价值。方法 采用红色荧光素（Spectrum Red标记的酵母人工染色体（YAC）克隆854E2[跨越第16号染色体短臂inv（16）断裂点]作为探针，用单色间期FISH检测26例急性粒－单核细胞白血病（AML－M4）inv（16)。在9例inv（16）患者中，特征性的3个红色荧光信号的阳性率仅为13.3%－32.1%（中位数21.3%）。结论 YAC854E2和间期FISH是检测inv(16)的有效方法。     

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。     

伴有t(11;20)(p15;q11)易位急性单核细胞白血病患者的细胞遗传学和分子遗传学研究

目的 :报道 1例伴有t(11;2 0 ) (p15 ;q11)易位的急性单核细胞白血病 (AML -M 5 )病例及其染色体涂染、逆转录-聚合酶链反应 (RT -PCR)的研究结果。方法 :骨髓细胞经直接法或 2 4h培养法常规制备染色体标本 ,以R显带技术进行核型分析 ;以 11号和 2 0号整条染色体涂染探针进行染色体涂染 ;采用RT -PCR技术检测NUP98-TOP1融合基因的转录本。结果 :R显带和全染色体涂染的结果证实该患者染色体异常为t(11;2 0 ) (p15 ;q11) ;RT -PCR检测到NUP98-TOP1融合基因的转录本。结论 :染色体涂染和RT -PCT技术的应用有利于检出t(11;2 0 ) (p15 ;q11)。     

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。     

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.     

一株伴有t(6;11)(q27;q23)和p53基因异常的人单核细胞白血病细胞系SHI-1的建立及鉴定

目的建立人急性单核细胞白血病(AML—M5b)细胞系并研究其生物学特性。方法从1例AML—M5b患者白血病复发时的骨髓标本分离出单个核细胞，用液体培养法进行培养。采用瑞特染色、电子显微镜、细胞化学染色、流式细胞仪、R显带核型分析、逆转录-聚合酶链反应(RT—PCR)、荧光原位杂交(FISH)、半固体甲基纤维素集落培养、裸小鼠致瘤实验、荧光定量PCR、DNA荧光染色法及支原体肉汤培养法、短串联重复序列(STR)-PCR、p53基因的PCR扩增产物测序、多色FISH(M—FISH)和^3H—TdR掺入实验等方法对SHI-1细胞的生物学特性进行了鉴定、结果建立了1个可持续增殖的人单核细胞白血病细胞系SHI-1；形态学和免疫表型呈现典型的单核系特征；核型分析显示SHI-1细胞系有和患者复发时骨髓细胞完全相同的异常：46，XY，t(6；11)(q27；q23)，del(17)(p11)；RT—PCR检出MLL—AF6融合基因的转录本；FISH俭测结果显示存在6号和11号染色体之间易位、MLL基因的重排和p53基因的缺失；PCR产物测序结果显示1个p53等位基因6号外显子发生点突变ATC→ACC集落培养显示SHI-1细胞具有较强的集落形成能力；皮下接种4只裸小鼠均形成实体肿瘤；荧光定量PCR提示无EB病毒感染；DNA荧光染色法和支原体肉汤培养法术检出支原体；M—FISH证实传代至2003年3月的SHI-1细胞除有t(6；11)、del(17)(p11)外，还有t(7；13)所致的衍生7号染色体、18单体和来自8号染色体的微小体；STR—PCR结果显示SHI-1细胞系确实来自患者原代白血病细胞；IL4-和IL-15可促进SHI-1细胞的增殖，IFN-1、TNFα、IL-2、PDGF和IL-7可抑制SHI-1细胞的增殖。结论SHI-1是1个伴有t(6；11)(q27；q23)和P53基因异常的裸小鼠高致瘤性人单核细胞白血病细胞系，为白血病研究提供了一个新的有价值的工具。     

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.     

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。     

Coding sequences of the tal-1 gene are disrupted by chromosome translocation in human T cell leukemia

The tal-1 proto-oncogene encodes a helix-loop-helix DNA-binding protein that has been implicated in the formation of T cell acute lymphoblastic leukemia (T-ALL). Patients with T-ALL harbor structural rearrangements of tal-1 that result from either local DNA deletion or t(1;14)(p34;q11) chromosome translocation. By analyzing t(1;14)(p34;q11) chromosomes from a series of patients, we have now identified a discrete region of tal-1 wherein most of the translocation breakpoints occur. Moreover, mapping of tal-1 genomic DNA revealed that coding exons are situated on both sides of the t(1;14)(p34;q11) major breakpoint region. Hence, the translocated allele of tal-1 is truncated in a manner that reduces its amino acid coding potential.     

Fluorescence in situ hybridization analysis of immunoglobulin heavy chain translocations in plasma cell myeloma using intact paraffin sections and simultaneous CD138 immunofluorescence

Fluorescence in situ hybridization (FISH) studies are much more sensitive than classical cytogenetics for identification of karyotypic abnormalities in plasma cell myeloma. However, FISH analysis of bone marrow samples is often challenging because of a large number of admixed non-neoplastic hematopoietic elements. In this report, we describe a novel method using FISH analysis of intact paraffin sections of formalin-fixed, bone marrow clot preparations with simultaneous CD138 tyramine signal amplification (TSA)-mediated immunofluorescence. We studied 22 cases of plasma cell myeloma for translocations involving the immunoglobulin heavy chain locus that are of known diagnostic and/or prognostic significance. All cases were analyzed using dual color, break-apart immunoglobulin heavy chain probe and dual color, dual fusion probes for t(11;14)(q13;q32) and t(4;14)(p16;q32). TSA-mediated fluorochrome deposition in CD138+ cells was unaltered by protease pretreatment. Translocations were identified in 10 cases, including five with t(11;14)(q13;q32) and three with t(4;14)(p16.3;q32). When present, abnormalities were identified in a large percentage of CD138+ cells (47 to 93%, median 84%). This technique allows for efficient molecular cytogenetic analysis of plasma cell myeloma using routinely archived paraffin-embedded material.     

伴有t(6;9)(p23;q34)/DEK-NUP214融合基因阳性的急性髓系白血病患者的特征分析

目的探讨伴有t(6;9)(p23;q34)/DEK-NUP214融合基因阳性的急性髓系白血病(AML)患者的特征。方法应用流式细胞术对8例初诊AML患者进行免疫分型;8例初诊AML患者的骨髓细胞培养24 h后按常规制备染色体,利用G显带技术进行染色体核型分析;采用实时荧光定量PCR的方法扩增DEK-NUP214融合基因。结果8例患者均异常表达AML抗原谱(主要包括HLA-DR、cMPO、CD33、CD13、CD34、CD11b、CD117);8例AML患者均形成DEK-NUP214融合基因,6例伴t(6;9)(p23;q34)易位,4例进行基因突变检测患者中,2例检出FLT3-ITD突变阳性;在中国人民解放军空军军医大学第一附属医院/西京医院住院治疗的5例患者中,1例未化疗即死亡,2例患者第1疗程用IDA标准剂量化疗,1例无效死亡,1例死于感染;2例行地西他滨联合CAG方案化疗,1例缓解后行异基因造血干细胞移植术,术后1.5年死于肺部感染,1例缓解后很快复发死亡。结论伴有t(6;9)(p23;q34)/DEK-NUP214融合基因阳性的AML是一类独特的、预后极差的急性白血病,检测DEK-NUP214融合基因有助于这类疾病的诊断、危险度分层、疗效观察和预后判断。     

核心结合因子相关急性髓系白血病的治疗进展

核心结合因子相关急性髓系白血病(core-binding factor acute myeloid leukemia,CBF-AML)是指一组以染色体t(8;21)(q22;q22)或inv(16) (p13.1q22)/t(16;16) (p13.1;q22)异常为特征的白血病亚型,是AML最常见的亚型之一.t(8;21)易位形成融合转录本AML1-ETO,而inv(16)/t(16;16)形成融合转录本CBFβ-MYH11.两种易位(倒位)都与核心结合因子(core binding factor,CBF)复合物相关.t(8;21)破坏了CBF复合物的α亚基,而inv(16)/t(16;16)破坏了CBF复合物的β亚基,两种易位都会影响正常CBF复合物的功能,进而对正常造血细胞的增殖、分化和凋亡造成干扰.近年来随着在分子机制、治疗、靶向药物、预后监测等方面的不断研究,CBF-AML在发病机制、化疗、靶向药物、造血干细胞移植等方面取得了很大进展,现将有关CBF-AML的研究进展做一综述.