伴有t(8;21)变异易位的急性髓系白血病患儿二例遗传学研究

 【摘要】　目的　报道2例分别伴有t(8;20)(q22;q13)和t(1;8;21) (q32;q22;q22)的t(8;21)变异易位的M2型急性髓系白血病（AML-M2）。方法　骨髓细胞短期培养法制备染色体标本,应用反带和吉姆萨显带技术进行核型分析;双色双融合AML1-ETO探针进行间期及中期双色荧光原位杂交（D-FISH）检测AML1-ETO融合信号;多重巢式反转录-聚合酶链反应（ RT-PCR）技术检测AML1-ETO融合基因转录本。结果　例1 核型为45,X,-Y, t (8;20)(q22;q13) [12]／46,XY[3],例2 核型为46,XX,t(1;8;21)(q32;q22;q22)[18]／46,XX[2];间期和中期FISH证实了AML1-ETO融合基因和变异易位的存在;多重巢式RT-PCR检测到AML1-ETO融合基因转录本。结论　t(8;20)(q22;q13)和t(1;8;21)(q32;q22;q22)实质上都是t(8;21)的变异型易位;核型分析联合D-FISH、多重巢式RT-PCR对确定伴有变异型t(8;21)易位的AML患者的性质和预后是重要的。     

伴t（16;21）（p11;q22）急性髓系白血病二例并文献复习

目的 探讨伴有t（16;21） （p11;q22）急性髓系白血病（AML）的临床及实验室检查特征.方法 对2例伴t（16;21）（p11;q22） AML患者分别进行骨髓形态学瑞特-吉姆萨染色、细胞化学染色、免疫学表型检测、常见基因筛查及遗传学检查,分析其临床及实验室检查的异同点,并复习相关文献.结果 例1 FAB形态学分型为AML-M4,其遗传学改变为：46,XY,t（16;21）（p11;q22） [16]/47,XY,t（16;21）（p11;q22）,＋21[4];例2为AML-M1,遗传学改变为46,XX,t（16;21）（p11;q22） [20].2例患者原始细胞均高表达CD56,均可见原始细胞吞噬自身血细胞现象.2例患者均于发病2年内死亡.结论 伴t（16;21）（p11;q22） AML有其独特的形态学、免疫表型、遗传学异常和临床表现,预后差,造血干细胞移植可能为其首选的治疗方法.     

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。     

异常复杂核型改变的骨髓增生异常综合征——难治性贫血伴环形铁粒幼细胞增多一例

 目的　探讨细胞遗传学在骨髓增生异常综合征（MDS）中的重要意义。方法　对1例应用骨髓细胞形态学诊断为MDS-RAS的患者分别进行常规染色体反带核型分析和白血病细胞分化抗原检测。结果　患者原始粒细胞占0.03,红系有明显的病态造血,环形铁粒幼细胞占0.20;流式细胞术检测原始细胞群占0.036,CD34、CD33、CD117阳性,CD13部分阳性;染色体分析为44,XX,der(5)add(5)(q33),del(7)(q22),add(9)(p23),der(10)add(10)(q21),del(12)(p12),add(16)(q23),-17,-22[14]/46,XX[6]。结论　该病例具有异常复杂的核型改变,在MDS-RAS中尚属少见,且在国际预后评分系统（IPSS）中占较大的分值,提示细胞遗传学检查对MDS的诊断和治疗具有重要意义。染色体的异常可能要早于骨髓形态学和白细胞表面分化抗原的变化,能及早监测疾病的进展和转变。     

261例急性髓系白血病的WHO分型

目的对急性髓系白血病(AML)患者的WHO分型系统进行评价。方法对按FAB标准确诊并进行了染色体核型分析和/或AML特异相关融合基因检测的259例AML和21例RAEB蛳t患者,重新分类计数其血片和骨髓片,按WHO标准回顾性进行分型诊断,并进行了按WHO标准分型诊断后各亚型之间的诱导化疗疗效比较。结果21例RAEB蛳t患者中2例按WHO标准重新诊断为AML。AML伴(t8;21)/AML1蛳ETO与按国内AML标准确诊的M2b、AML伴t(15;17)/PML蛳RARα与M3/M3v、AML伴inv(16)(p13q22)或t(16;16)(p13;q22)/CBFB蛳MYH11与M4Eo的吻合率为100%。21例(11.2%)的患者重新归入AML伴有多系发育异常。AML伴t(8;21)/AML1蛳ETO和AML伴inv(16)(p13q22)或t(16;16)(p13;q22)/CBFB蛳MYH11患者的诱导化疗CR率显著高于不另做分类的AML患者(P<0.05)。有多系增生异常患者的诱导化疗CR率明显低于无多系增生异常患者(P<0.05)。结论AML的WHO分型各亚型的一致性及与临床疗效相关性较FAB分型更好。     

多重荧光原位杂交在多发性骨髓瘤复杂核型异常检测中的应用

目的探讨多重荧光原位杂交(m u ltip lex fluorescence in s itu hybrid ization,M-F ISH)在多发性骨髓瘤(m u ltip le m ye lom a,MM)复杂核型异常(com p lex chrom osom a l aberrations,CCA s)检测中的价值。方法联合应用常规细胞遗传学(conven tiona l cytogenetics,CC)方法及M-F ISH分析2例伴有复杂核型的MM患者。结果M-F ISH证实了MM原有的异常染色体+5,+7,+9,-13,+15,de l(6)(q16q26),add(2)(p25),der(4)t(4;?)(p11;?),add(22)(q11),并确定了add(2)(p25),der(4)t(4;?)(p11;?),add(22)(q11)的具体来源;同时也发现了CC分析未能发现或不能识别的der(6)t(6;17)(q?;?),der(7)t(1;7)(?;q21)×2,de l(9)(q21),der(9)t(1;9)(?;q21),de l(16p12),充分显示了M-F ISH的优越性。结论M-F ISH对于检测MM的CCA s具有优势,是精确分析染色体核型不可缺少的技术。     

乙亚胺治疗银屑病导致1例以t(11;19)(q23;p13)为特征的治疗相关性急性髓系白血病

目的：报道1例乙亚胺治疗银屑病导致以t(1l；19)(q23；p13)为特征的急性髓系白血病(AML-M4)。方法：骨髓细胞24h培养后按常规制备染色体，用R显带技术进行核型分析，并以ll号、19号染色体涂抹探针和位于llq23的混合谱系白血病(AML)基因单一序列探针进行荧光原位杂交(FISH)检测。结果：染色体分析20个中期分裂相．其中15个t(11；19)(q23；p13)为唯一异常，5个除此以外，同时伴有der(6)t(?；6)(?；p24)；染色体荧光原位杂交(FISH)检测证实1条ll号染色体和1条19号染色体之间发生了相互易住，并且FISH检测揭示MLL基因重排细胞占58．4％．结论：二氧哌嗪类药物除了可诱发AMLt(15；17)M3型和t(8；21)、t(7；11)M2型之外，还可诱发t(1l；9)M4型．     

遗传学和免疫表型分析在急性粒单核细胞白血病临床诊断中的意义

 目的　探讨染色体G显带、荧光原位杂交和流式细胞术在急性粒单核细胞白血病临床诊断、鉴别诊断和预后中的意义。方法　运用染色体G显带和流式细胞术 ,对 15例骨髓细胞形态学拟诊为急性髓系白血病M4型 (AML M4 )的患者进行核型分析和免疫分型 ,并用间期荧光原位杂交技术 (inter phasalfluorescenceinsituhybridization ,I FISH)对其中 6例患者进行检测。结果　染色体G显带核型分析显示正常核型 6例 ,伴有inv(16 ) (p13;q2 2 )异常 2例 ,伴有del(16 ) (q2 2 )、 X ,5 q ,t(8;2 1) (q2 2 ;q2 2 )、t(9 ;2 2 ) (q34;q11)、t(11;17)和t(11;?)异常各 1例 ,另有 2例无分裂相可供分析。I FISH对 3例患者进行CBFβ基因重排检测 ,2例阳性 ,1例阴性 ;对这例阴性患者进一步检测AML1/ETO融合基因 ,结果阳性 ;3例患者检测了MLL基因重排 ,2例阳性 ,1例阴性但伴有t(9;2 2 )异常 ,BCR/ABL融合基因阳性。免疫分型提示 14例患者有髓系和单核系分化抗...     

伴复杂染色体异常的套细胞淋巴瘤-例并文献复习

报道伴复杂染色体异常的套细胞淋巴瘤(MCL)1例并复习相关文献.患者男,58岁.发现全身肿块1年余,常规染色体核型为92,XXYY,7q ×2,9q ×2,t(11;14)×2,13q-×2,15q ×2/46,XY[8].I-FISH示t(11;14),M-FISH示89,XXYY, 1, 1, 2, 2, 3, 3, 4, 4, 5, 5, 6, 6, der(6)t(6;8), 7, der(7)t(7;9), 8, 8,der(9)t(9;15)×2. 10, 10, del(11)(q?)×2, 12, 12, der(13)t(3;13)×2, der(14)t(11;14)×2, 16, 16, 17, 17, 18, 18, 19, 19, 20, 20, 21, 21, 22, der(22)t(4;22)[20]/46,XY[11].骨髓涂片示原始淋巴细胞22.8%,幼稚淋巴细胞10.0%,免疫表型示原幼淋巴细胞占39.9%,CD19 90%;二次摄门CD19 细胞表达:CD5 89.5%,CD20 100%,CD23阴性;淋巴结免疫组化Cyclin Dl 、CD43 、CD10-.Hyper-CVADA及B方案交替化疗后全身肿决消失,复查骨髓:原幼琳占0.8%,流式细胞检查未见微小病灶残留(MRD),FISH结果示t(11;14)阳性细胞0/200.初步研究结果提示,对少见复杂表现的小细胞淋巴瘤可以先借助组织学和免疫表型改变来诊断大部分的病例.     

伴有t(4;12)(q11-12;p13)易位的急性微分化型髓系白血病1例

目的 报道1例罕见的伴有t(4;12)(q11．12;p13)易位的急性微分化型髓系白血病(AMI—M0)病例。方法 应用流式细胞仪检测患者白血病细胞的胞质抗原MPO,CyCD79a;采用骨髓短期培养法,按常规制备染色体,应用R显带技术进行核型分析及应用4号和12号全染色体涂染探针对该病例进行分析。结果 形态学和免疫表型检测证实该病例为．AML-M0;染色体核型分析揭示该病例伴有t(4;12)(q11．12;p13)易位;全染色体涂抹分析证实1条4号染色体和12号染色体之间发生了相互易位。结论 t(4;12)(q11．12;p13)易位与AML-M0有着一定的相关性;具有该种易位的病例生存期短,预后差;全染色体涂抹技术是一种有效的检测手段。     

Karyotypic aberrations in an anal-canal malignant-melanoma and its local metastasis

Tissue samples from a malignant melanoma of the anal canal and its local metastasis were short-term cultured and analyzed cytogenetically. Complex chromosome aberrations were found in the primary tumor, yielding the karyotype 49-50,X,-Y,der(1)t(1;13)(q44;q12),+der(2)t(2;8) (q31;q12),der(6)t(5;6)(q13;q21),+del(6)(q12q21),+7, der(8)t(6;8)(p12;p21),del(11)(p11),der(11)t(11;12) (p15;q24),der(15)t(6;15)(p21;p11-13),+der(20)t(1;20) (q12;q13),der(22)t(11;22)(p11;p11)[34]/88-100,idemx2[3]. In the local metastasis, the same near-tetraploid abnormal clone was detected, indicating that the cell population was clonally stable during tumor progression. This is the first malignant melanoma of the anal canal that has been cytogenetically characterized.     

急性髓系白血病伴新的t(8;21)变异易位——t(7;21)(p21;q22)易位

目的:探讨1例急性髓系白血病(acute myeloid leukemia,AML)伴新的t(8; 21)变异易位即t(7; 21)(p21;q22)易位患者的临床与分子生物学特点.方法:将AML患者的骨髓细胞经短期培养后按常规方法制备染色体,R显带进行核型分析;利用AML1/ETO双色双融合探针进行荧光原位杂交检测;实时荧光定量PCR法检测AML1/ETO融合基因的转录本拷贝数.结果:患者的常规细胞遗传学分析结果显示为t(7; 21)(p21;q22)易位.86％的骨髓细胞为AML1/ETO融合基因阳性,融合基因转录本为51 440个拷贝/10 000个内参Ab1基因拷贝.结论:t(7;21)(p21; q22)是一种新的t(8; 21)(q22; q22)变异易位,与其他类型的t(8; 21)变异易位相似,预示有良好预后.     

Cytogenetic findings in pediatric radiation-induced atypical meningioma after treatment of medulloblastoma: case report and review of the literature

Ionizing radiation is the most recognized risk factor for meningioma in pediatric long-term cancer survivors. Information in this rare setting is exceptional. We report the clinical and cytogenetic findings in a radiation-induced atypical meningioma following treatment for desmoplastic medulloblastoma in a child. This is the second study to describe the cytogenetic aspects on radiation-induced meningiomas in children. Chromosome banding analysis revealed a 46, XX, t(1;3)(p22;q12), del(1)(p?)[8]/46, XX[12]. Loss of chromosome 1p as a consequence of irradiation has been proposed to be more important in the development of secondary meningiomas in adults. Deletions in the short arm of chromosome 1 also appear to be a shared feature in both pediatric cases so far analyzed.     

5q− syndrome and multiple myeloma diagnosed simultaneously and successful treated with lenalidomide

A 72-year-old woman was diagnosed with 5q− myelodysplastic syndrome in the course of an indolent multiple myeloma (MM). Bone marrow (BM) cytogenetics disclosed two unrelated clones: 46,XX,del(5)(q13q33), and [47,X,-X,der(1;21)(q10;q10),−4,−4,+5,del(5)(q13q31),+7,der(7)t(1;7)(p34.2;p22),add(8)(p23),−13,+15,der(16) t(1;16)(q23;q12.2),+19,−21,+mar1,+mar2]. The last complex karyotype belonged to malignant plasma cells. FISH and SKY techniques demonstrated different 5q deletions. EGR1 gene (on 5q31) lost in 5q− syndrome remained in 5q− plasma cells. Biclonal evolution was noted: myeloid 5q− cells added a deletion 13q and plasma cells showed monosomy 13. Patient achieved complete cytogenetic response of 5q− syndrome with low-dose of lenalidomide, and a partial remission of MM with high-dose of lenalidomide/dexamethasone combination.     

Trisomy and tetrasomy for long arm of chromosome 1 in near-diploid human endometrial adenocarcinomas

Karyotypic analysis by R-banding after short-term culture, carried out on 7 cases of human endometrial adenocarcinoma, showed in 4 of these a trisomy or a tetrasomy for the long arm of chromosome I. In the 4 cases, these imbalances were due to rearrangements involving centromeric or para-centromeric break-points: 46,XX,-16, +der(1q16p) t(1;16)(1p16q;1q16p); 46,XX,-21, +der (1q21q)t(1;21) (1p21p;1q21q); 46,XX, -21, +der(21) t(1;21)(q11;p13); 48, XX, +2, +i(1q). Two other cases showed only a numerical aberration: 47, XX, +10 and 47, XX, +12. In the last case, only cells with apparently normal karyotype were seen. In the 4 cases with an anomaly of chromosome I, two normal I chromosomes coexisted with abnormal elements. This shows that the rearrangement very likely occurred in G2 phase of the cell cycle.     

Variant Philadelphia translocations in chronic myeloid leukemia: correlation with cancer breakpoints, fragile sites and oncogenes

Four cases of variant Philadelphia (Ph1) translocations were found in 72 patients (5.5%) with Ph1-positive chronic myeloid leukemia (CML). One previously unreported case was a simple variant translocation, namely, 46,XY,t(11;17)(q13;p13),t(17;22)(q25;q22); 46,XY,t(1;21)(q32;q11),t(11;17)(q13;p13), t(17;22)(q25;q11). Complex variant translocations were observed in three cases, namely, 46,XY,t(5;9;22)(q31;q34;q11),46,XX,t(8;9;22) (q22;q34;q11) and 46,XX,t(9;15;22) (q34;q15;q11). The chromosomal breakpoints in the cases of variant Ph1 translocations were the following: 1q32, 5q31, 8q22, 11q13, 15q15, 17p13, 17q25 and 21q11. Eight of the eight (100%) breakpoints were located in Giemsa-negative bands. Furthermore, seven of the eight (87%) variant Ph1 breakpoints correspond to the breakpoints present in consistent cancer arrangements. Three of the eight (38%) correspond to fragile sites and four of the eight (50%) correspond to oncogenes.     

Secondary chromosome changes in mantle cell lymphoma: cytogenetic and fluorescence in situ hybridization studies.

To better define the incidence and nature of secondary chromosome anomalies in mantle cell lymphoma (MCL) carrying the t(11:14)/BCL1 rearrangement, cytogenetic and fluorescence in situ hybridization studies (FISH) were performed in 42 patients (39 classical histology, 3 blastoid variant), using 6q21, 9p21/p16, 13q14, 17p13/p53 and chromosome-12-specific probes. Karyotypes from 89 cases published in 5 recent series including patients diagnosed in a homogeneous fashion were reviewed. In our series, FISH confirmed the interpretation of the karyotype in all cases and disclosed cryptic chromosome deletions in a sizeable fraction of cases. One patient (2.4% of total) was found with a cryptic 9p21 deletion by FISH. Two cases (4.8%) had a 6q21 deletion at CCA and at FISH; +12 was found in three cases by CCA plus nine by FISH (28.6%); 13q14 deletion was found in six cases by CCA plus 16 by FISH (52.4%), 17p13 deletion in three cases by CCA plus 8 by FISH (26.2%). In 131 patients (42 present series plus 89 in the literature) secondary chromosome aberrations seen by conventional cytogenetic analysis in more than 5 cases included deletions/translocations (del/t) 6q15-23 [15 cases]; -13 [14 cases]; del/t 1p21-31 [12 cases]; +3q [11 cases]; del/t 17p [9 cases]; 8p translocations and del(Y) [8 cases each]; -20 [7 cases]; 13q14 deletion, del/t 11q22-23, del/t 9q, del(10)(q22q24), -20, -21, -22 and -X [6 cases each]. We arrived at the following conclusions: i) though no secondary anomaly is specific for MCL, there is a distinct profile of recurrent chromosome lesions in MCL with 1p21-31 deletions, 8p translocations, 11q22-23 anomalies having a strong association with CD5+ B-cell lymphomas of low-to-intermediate grade histology; ii) FISH enabled the detection of cryptic chromosome 12, 13q and 17p rearrangements in a sizeable fraction of cases; iii) 9p21/p16 deletions did not occur at a high incidence in this series, possibly because of the low number of cases with blastoid variant.     

A complex karyotype involving chromosomes 3, 6, 11, 12, and 22 in adult acute lymphoblastic leukemia

Complex chromosomal abnormalities are rare in adult patients with acute lymphoblastic leukemia (ALL). Using molecular methods, we characterized a complex karyotype involving chromosomes 3, 6, 11, 12, and 22 in a 38-year-old man with ALL. Cytogenetic analysis revealed the following karyotype: 46,XY,der(3)t(3;?6)(q22;?p21), - 6,add(11)(q23),add(12)(p13), + mar[10]/46,XY[19]. Because patients with 11q23 abnormalities have a poor prognosis and require aggressive treatment, we used fluorescence in situ hybridization (FISH) to fully characterize the abnormalities. FISH analysis showed no rearrangement of the MLL or ETV6-CBFA2 (TEL-AML1) genes; the wild-type ETV6 allele was deleted in most cells. The revised karyotype after the FISH analysis was as follows: 46,XY,der(3)t(3;12)(p13;p?13)del(3)(q21),der(6)inv(6)(p21q21)ins(6;3)(q21;q21q25),der(11)t (3; 11)(q25;q23),der(12)t(11; 12)(q23;p?12),t(12;22)(p13;q13). Although structural abnormalities involving 11q23 and 12p13 bands were identified by conventional cytogenetics, this report clearly demonstrates that molecular assays are needed to fully characterize gene rearrangements, complex translocations as well as to assign patients to the appropriate treatment group.