一例伴有der（2）t（2：15）（q37；q22）的急性早幼粒细胞白血病的临床及实验研究

目的研究1例der（2）t（2：15）核型异常的急性早幼粒细胞白血病（AFL）的临床和实验特征。方法对1例初发的老年APL患者进行流式细胞术免疫分型、传统细胞遗传学分析,并应用双色荧光原位杂交（FISH）明确染色体异常。结果该患者染色体核型为46xy,der（2）t（2;15）（q37;q22）,der（15）t（15;17）（q22;q10）[9]／47,xy,＋y【1】,FISH检测同一细胞中出现一个PML—RARα融合信号。免疫表型高表达CD13、CD33、MPO。结论der（2）t（2;15）是APL中罕见的核型异常,FISH是确认染色体异常的可靠手段。     

荧光原位杂交检测骨髓增生异常综合征患者染色体复杂核型变化及临床意义的研究

目的:探讨骨髓增生异常综合征(MDS)患者复杂核型变化及其临床意义。方法:在常规细胞遗传学(CC)方法检测基础上,运用荧光原位杂交技术(FISH),采用多种位点特异性DNA探针(染色体全染、特殊位点、双色易位融合探针)对35例MDS患者进行染色体核型分析。结果:35例MDS患者中有24例出现染色体异常,包括染色体数目及结构的异常,阳性率占68.6%。其中6例出现5号染色体单体或5号染色体长臂丢失;4例出现7号染色体单体或7号染色体长臂丢失;1例出现等臂7号染色体;2例出现8号染色体三倍体;3例出现Y染色体丢失;2例出现16号染色体倒位;5例出现复杂的染色体易位,包括t(6;?),(t8;21)(q22;q22),(t7;?),der(19)(t19;?)(q13.3;?),der(9)(t9;?)(p11;?)(t6;9),(t8;14),(t1;8)。结论:FISH技术在MDS染色体核型分析上可作为重要技术补充手段弥补CC检查的不足,对MDS准确诊断分型、合理治疗方法的选择乃至对预后的评估都具有重要的临床意义。     

急性髓性白血病混合谱系白血病基因重排的研究

目的对急性髓性白血病(AML)患者可能出现的混合谱系白血病(mixed lineage leukemia,MLL)基因重排进行研究,并探讨其临床意义。方法在常规细胞遗传学分析基础上运用分子生物学方法-荧光原位杂交技术(FISH),采用多种位点特异性DNA探针(染色体全染、特殊位点、双色或多色易位融合探针),对58例AML患者(47例成人AML,11例儿童AML)进行分析研究。结果有6例出现MLL基因重排,分别出现MLL基因的移位,复制及丢失,阳性率占10．3％。其中4例为成人AML,2例为儿童AML,除了MLL基因重排外,5例AML患者同时合并有复杂的核型变化,分别为:47-48,XX,der(1)t(1;17)(p36．1;q23),+4,+10,der(11)t(11;17)(q23;q23),-17,-18, +20,+21?.ish+21(wcp21+),der(1)t(1;17)(wcp17+),der(11)t(11;17)(wcp11+;wcp17 +);46,XX,del(5)(q13q33),r(11)(p15q25),+r(11)(p15q25)．ishr(11)(wcp11+,MLL+),+r (11)(wcp11+,MLL+);46,XY,del(11)(q23)[2]／46,idem,add(16)(p13．1)[8]／46,XY[10]．ishadd(16)(wcp16+),rea(11)(wcp11+);55,XY,+ markers．ish 11q23(MLL×3),+21(wcp21 +);46,XY,add(11)(q23)[6]／46,idem,t(15;17)(q22;q21)[12]／46,XY[2]．ish dup(11)(MLL ++),t(15;17)(PML+,RARa+;RARa-)[24]。结论急性髓性白血病常合并有MLL基因重排,本实验组的阳性率超过10％。由于MLL基因重排的患者具有对常规化疗不敏感及预后不良的特点,对初治急性白血病患者应常规进行MLL基因重排的检查。     

30例儿童急性粒细胞白血病M2亚型细胞遗传学分析

目的了解儿童急性粒细胞白血病(AML)M2亚型遗传学特征.方法初步分析30例儿童AML-M2的染色体核型变化.结果 30例儿童AML-M2染色体核型中伴t(8;21)(q22;q22)组占46.67%(14/30),正常核型组占36.67%(11/30),其它异常核型组占16.66%(5/30),其中有1例为罕见的伴t(8;21)(q22;q22)的亚四倍体核型.结论证实了t(8;21)易位染色体为儿童AML-M2亚型较为特征性的遗传学变化.     

染色体和遗传

061474 性染色体异常核型37例细胞遗传学分析；061475 17例9号染色体臂间倒位遗传学分析；061476 排卵后老化对卵母细胞姐妹染色单体平衡性早分离的影响;061477 产前诊断48，XY，＋21，＋22和48，XY，＋7，＋8各1例；061479 46，XY，t（1；17）（q23；q25）伴流产畸胎1例。     

应用M-FISH技术检测急性髓细胞白血病的两种新的复杂变异性t(8;21)易位

目的：探讨M-FISH技术在检测复杂核型中的价值。方法：联合应用常规细胞遗传学技术和M-FISH检测2例伴有复杂核型异常的急性髓细胞白血病患者。结果：常规细胞遗传学技术检测2例急性髓细胞白血病患者的核型分别是：病例1为46。xy，der（8）t（8；21）。＋mar；病例2为46。xx．r（1）（p36p11）。del（5）（q22q34）der（8）t（8；21），＋mar。而应用M-FISH检测2例中的标记染色体分别是：t（8；21；8）和t（21；8；18；1）。例1经过1次诱导缓解治疗未获得完全缓解．并很快死亡。例2在4次不同方案的诱导缓解治疗后才获得完全缓解。结论：M-FISH是一种有效的检测复杂核型异常的方法。伴有复杂变异的t（8；21）核型的AML患者预后似乎不良。     

八探针间期荧光原位杂交技术联合染色体核型分析比较成人与儿童急性淋巴细胞白血病患者的细胞遗传学差异

应用八探针间期荧光原位杂交技术（FISH）联合染色体核型分析观察急性淋巴细胞白血病(ALL)成人患者与儿童患者的细胞遗传学差异。方法 对125例ALL患者（成人86例、儿童39例）全部行八探针FISH（MYC、P16、E2A、TEL/AML1、BCR/ABL、MLL、IGH、多倍体的 DNA 探针）检测并染色体核型分析。结果 八探针 FISH 检测结果显示,成人 ALL 患者与儿童 ALL患者的TEL/AML1融合基因、BCR/ABL融合基因与多倍体阳性率之间的差异有统计学意义（P<0.05）;染色体核型分析成人ALL患者与儿童ALL患者的（t9;22）易位、多倍体阳性率之间的差异有统计学意义（P<0.05）。结论 成人ALL患者与儿童ALL患者融合基因表达各有侧重,不同的细胞遗传学特征与其预后密切相关。FISH多探针诊断系统检测ALL患者常见遗传学异常省时、准确、高效,与染色体核型分析形成很好的互补。     

伴染色体结构异常的骨髓增生异常综合征

目的研究伴染色体结构异常的骨髓增生异常综合征（MDS）患者的临床和实验室特点。方法584例有可分析细胞遗传学资料的MDS患者,对其中有染色体结构异常患者按WHO标准重新进行诊断分型,对这些患者的临床和实验室特点进行回顾性分析。结果MDS患者染色体结构异常发生率为7．4％,常见染色体结构异常有i（17）（q10）、t（1;3）（p36;q21）、der（1;7）（q10;p10）和der（22）,另13例患者的染色体结构异常迄今尚无文献报道。i（17）（q10）患者表现中、重度贫血,骨髓易见粒系核左移,少颗粒,假Pelger—Hiiet异常及淋巴样小巨核,多为单纯核型异常,预后差。t（1;3）（p36;q21）患者表现大细胞性贫血,骨髓可见粒系成熟障碍,单核细胞比例高,巨核系病态增生,以MEL1基因表达为主或仅表达MEL1。der（1;7）（q10;p10）患者多以感染起病,大细胞或正细胞性贫血,骨髓三系病态造血,中位生存期短。der（22）患者表现贫血,血小板不低,骨髓可见粒系少颗粒,假Pelger-Hiiet异常及单元核、双元核巨核细胞,伴累及22q11的易位。结论伴i（17）（q10）、t（1;3）（p36;q21）和der（1;7）（q10;p10）的MDS可能为独立的临床病理遗传学病种,而der（22）尚有待更多的病例进一步证实。     

31例慢性粒细胞性白血病患者染色体追踪观察

目的探讨慢性粒细胞性白血病（CML）的染色体核型在病程中的变化与临床关系。方法采用24h、48h培养法制备骨髓染色体，G显带技术对31例Ph＋CML患者进行染色体核型追踪分析。结果有10例发生了新的额外染色体异常改变，占32．2%。额外染色体异常有＋12，＋15，＋21，18q＋，i（17q），r（2），r（17）等，以及两条染色体间的易位，这些出现二次染色体畸变病例多在检出新的额外染色体异常后半年左右因化疗不敏感或急变死亡。结论Ph＋CML患者在病程中出现额外染色体畸变，提示临床疗效差，预后不良。通过细胞遗传学染色体核型追踪分析有助于对CML临床疗效观察以及预后判断。     

急性髓细胞白血病的主要遗传学变异和临床意义

细胞与分子遗传学异常在恶性血液病中占有至关重要的地位,急性髓系白血病（AML）为一高度异质性疾病,目前报道与AML相关的染色体核型异常类型达100多种,许多特异性的遗传学改变已成为指导AML诊断与治疗的重要分子标志.少数特定遗传学标记如t（8;21）（q22;q22）易位,伴有inv（16）（p13;q22）和伴t（15;17）（q22;q11-12）易位的急性髓细胞白血病白血病预后相对较好,但更多的突变因素和复杂的染色体易位提示急性髓细胞白血病预后不良.     

Chromosomal changes detected by fluorescence in situ hybridization in patients with acute lymphoblastic leukemia

Objectives To investigate patients with acute lymphoblastic leukemia (ALL) for TEL/AML1 fusion,BCR/ABL fusion, MLL gene rearrangements, and numerical changes of chromosomes 4, 10, 17 and 21 by fluorescence in situ hybridization (FISH) and to determine the relationship and the significance of those findings.Methods Fifty-one American patients (34 men and 17 women) were included in this study. Of them there were 41 patients with pro-B cell type ALL, 9 with B cell type ALL and 1 with T cell type ALL.Chromosome metaphases of each sample were prepared according to standard protocols.Fluorescence in situ hybridization was performed using commercially available DNA probes, including whole chromosome painting probes, locus specific probes, specific chromosome centromere probes and dual color/multiple color translocation fusion probes. The digital image analysis was carried out using Cytovision and Quips FISH programs.Results An overall incidence of chromosomal anomalies, including t (9; 22 ), MLL gene rearrangements, t (12;21), and numerical chromosomal anomalies of chromosomes 4, 10, 17 and 21 was found in 33 patients (65%). Thirty-one of them were pediatric patients and two adults. The t(12;21) was the commonest chromosomal anomaly detected in this population; 14 out of the 45pediatric patients (31%) were positive for TEL/AML1 fusion, among which three had an additionalderivative 21[t (12;21) ], four had a deletion of 12p and two had an extra copy of chromosome 21.All 14 patients with positive TEL/AML1 fusion had ALL pre-B cell or B-cell lineage according to standard immunotyping. The percentage of cells with fusion signals ranged from 20% to 80%. All fourteen patients positive for TEL/AML1 gene fusion were mosaic. Three out of the 14 patients positive for the TEL/AML1 gene fusion were originally reported to be culture failures and none of the remaining eleven samples had been found to have chromosome 12 abnormalities by conventional cytogenetic techniques. All pediatric patients with pre-T or T cell lineage and the six adults were negative for TEL/AML1 fusion. One patient had double Philadelphia chromosomes, three had a rearranaement or a deletion of the MLL aene. one had t (4;11)and two had a deletion of the MLL One of the patients with an MLL deletion also had a large ring of chromosome 21, and r (21) was caused by AML1 gene tandemly duplicated at least five times. The second case with the MLL deletion was also unique, the patient had a t (12;21) as well. A total of 20 patients had numerical changes( gain or loss) of chromosomes 4, 10, 17 and 21. Eight patients were found to have trisomies of three or four different chromosomes. Interestingly, seven of these patients did not have TEL/AML1, BCR/ABL or the MLL aene rearranaement, one did have the TEL/AML1 aene fusion. Eleven patients with pro-B cell or B cell type ALL (9 children with ALL, 2 adults with ALL) had numerical changes of chromosome 21 (gain 1 or 2 chromosome 21 ), among them, 10 patients had no structural alteration of chromosome 21, and one was combined by t (12;21 ). Four patients had a monosomy of chromosome 17 and three out of these patients with monosomy 17 also had a fusion signal of TEL/AML1.     

Complex t(8;13;21)(q22;q14;q22)--a novel variant of t(8;21) in a patient with acute myeloid leukemia (AML-M2)

Variants of the t(8;21)(q22;q22) involving chromosome 8, 21, and other chromosomes account for about 3% of all t(8;21)(q22;q22) in acute myeloid leukemia (AML) patients. We report a case of AML-M2 with t(8;13;21)(q22;q14;q22), not reported earlier. Using a dual-color fluorescence in situ hybridization (FISH) analysis with ETO and AML1 probes, we demonstrate an ETO/AML1 fusion signal on the derivative chromosome 8. Whole chromosome painting probes were used for chromosomes 8 and 13, to demonstrate the three-way translocation t(8;13;21)(q22;q14;q22). Involvement of chromosome region 13q14 has never been reported earlier, although region 13q12 as a variant in AML with t(8;21) has been reported earlier. The possible role of genes in this region in leukemogenesis, its response to the treatment and its clinical implications are discussed.     

Supernumerary chromosome marker Der(22)t(11;22) resulting from a maternal balanced translocation

Derivative 22 [der(22)] syndrome is a rare disorder associated with multiple congenital anomalies including pre-auricular skin tags or pits, conotruncal heart defects, and profound mental retardation. Der(22)t(11;22) is one of the causes of supernumerary chromosome markers (mar) in humans. We present a boy with developmental delay and multiple anomalies consistent with the supernumerary der(22) syndrome. Cytogenetic analysis showed an abnormal chromosome complement of 47, XY, +mar in all 50 cells analyzed. The karyotype of his mother showed a reciprocal translocation over the distal bands 11q23 and 22q11, respectively, i.e., 46,XX,t( 11;22)(q23.3;q11.2), and that of his father was 46,XY. Thus, the nature of the supernumerary chromosome markers was of der(22)t(11 ;22)(q23.3;q11.2). The clinical features, including craniofacial dysmorphism, hypotonia, psychomotor retardation, heart defects, and urogenital anomalies, were the combined effects of partial trisomies for both distal 11q and pericentromeric 22q.     

慢性粒细胞白血病染色体异常的研究

目的 研究慢性粒细胞性白血病急变过程中基因组的异常,方法 对１５例急变期,３例加速期和２０例慢性期的患者进行了常规细胞遗传学分析,用比较基因组杂交和双色染色体涂抹的方法。结果 在所有被研究的病例中均检测到费城染色体,其中１５例演进病例中有１２例还伴有其它的染色体数量和／或结构的异常,而２０例慢性期中仅５例伴其它异常。染色体数量变化是Ｐｈ染色体双体或三体（５／１４例）和８号染色体三体（５／１４）,另     

A cytogenetic study of five rare karyotypes

Summary The results of chromosme analysis of 5 cases from our genetic counseling showed that among these patients, 4 had two or more repeated spontaneous abortions. Structural abnormalities with the karyotypes 46, XX, t(1;11)(q42;q13), 46, XY, t(l7:19)(q21;pl3.3), 46.XY, t(4;5)(p13;q35) were reported for the first time in the literature abroad. The karyotypes 46, XX, t(l6;18)(q24;q21), 46,XX, t(3;8)(p21;q24.3) were reported for the first time in the literature at home, A discussion is made on the origin of chromosome aberration and the cause of repeated spontaneous abortions.     

五例罕见异常核型的细胞遗传学研究

本文从遗传咨询中对5例患者作染色体分析,其中4例曾有2次或2次以上反复自然流产史,结果发现染色体结构异常46,XX,t(1;11)(q42;q13)、46,XY,t(17;19)(q21;p13.3)、46,XY,t(4;5)(p13;q35)为世界首报;46,XX,t(16;18)(q24;q21)、46,XX,t(3;8)(p21;q24.3)核型是国内首次报道。本文对染色体畸变及反复自然_流产的来源和原因进行了讨论。     

染色体4号长臂和9号短臂移位的遗传分析

目的 探讨母子4号和9号染色体移位的遗传效应。方法 无菌采集外周血,采用微量淋巴细胞培养法进行染色体制作,G显带分析染色体核型,并通过调查病史分析其遗传效应。结果 母亲染色体核型为46,XX,t（4;9）（q31;p24）,其子染色体核型为46,XY,der（9）t（4;9）（q31;p24）mat。其子的异常9号染色体是由母亲遗传而来。结论 母亲为染色体平衡移位携带者,患儿的异常9号染色体为母源的,该母亲出生正常后代的几率仅为1／18,故加强婚前和产前染色体检查对预防染色体病儿出生意义重大。